fluticasone and Asthma

The GINA recommends inhaled corticosteroids (ICSs) for the treatment of steps 2-3 of childhood asthma. However, the difference in efficacy between these drugs remains unclear. The purpose of this study was to compare the efficacy of different ICS drugs in the treatment of childhood asthma.. We searched PubMed and EMBASE for randomized controlled trials of ICSs in the treatment of childhood asthma. Using forced expiratory volume in the first second (FEV. Six studies involving 2237 children that reported FEV. In this study, the efficacy of three ICS drugs was quantitatively compared, providing necessary information for the implementation of medication guidelines for steps 2-3 of asthma in children.. This study analyzed the entire time-course of the drug efficacy of Inhaled corticosteroids in the treatment of asthma in children aged 5-12, which found that although the maximum efficacy of both ciclesonide and budesonide was the same, the onset speed of ciclesonide was faster than that of budesonide. The above information provides the necessary quantitative information for the implementation of medication guidelines for steps 2-3 asthma in children.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Fluticasone; Humans

Pharmacological asthma management focuses on the use of inhaled corticosteroid (ICS)-containing therapies, which reduce airway inflammation and provide bronchoprotection, improving symptom control and reducing exacerbation risk. ICS underuse due to poor adherence is common, leading to poor clinical outcomes including increased risk of mortality. This article reviews efficacy versus systemic activity profiles for various adherence patterns and dosing regimens of fluticasone furoate (FF)-containing and budesonide (BUD)-containing asthma therapies in clinical trials and real-world studies.. We performed a structured literature review (1 January 2000-3 March 2022) and mathematical modelling analysis of FF-containing and BUD-containing regular daily dosing in patients with mild-to-severe asthma, as-needed BUD/formoterol (FOR) in mild asthma, and BUD/FOR maintenance and reliever therapy (MART) dosing in moderate-to-severe asthma, to assess efficacy (bronchoprotection) and systemic activity (cortisol suppression) profiles of dosing patterns of ICS use in multiple adherence scenarios.. A total of 22 manuscripts were included in full-text review and 18 in the model simulations. Focusing on FF-containing or BUD-containing treatments at comparable adherence rates, regular daily FF or FF/vilanterol (VI) dosing provided more prolonged bronchoprotection and fewer systemic effects than daily BUD, daily BUD/FOR, or BUD/FOR MART dosing, especially in low adherence scenarios. In model simulations and the real-world setting, FF/VI generally provided longer bronchoprotection, lower systemic activity, and greater clinical benefits over BUD/FOR as well as consistently higher adherence.. In this literature review and modelling analysis, FF/VI was found to show clinical advantages on asthma control over BUD/FOR. These findings have implications for helping clinicians select the most suitable inhaled therapy for their patients with asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Fluticasone; Humans

This study aimed to evaluate the efficacy and safety of montelukast (Mon) + fluticasone propionate (Flu) versus Flu in the treatment of cough variant asthma (CVA) in children.. Eligible documents were selected from various databases. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to evaluate continuous variables, and categorical variables were evaluated using risk ratio (RR) and 95% CI. Heterogeneity analysis was performed using Cochran's Q test and I. Nine studies were included, and Flu + Mon was found to significantly improve the total effective rate and reduce cough recurrence compared to Flu. The cough remission and disappearance times in the Mon + Flu group were significantly lower than those in the Flu group. FEV1% recovery in the Mon + Flu group was significantly better than that in the Flu group.. Mon + Flu is effective and safe for the treatment of CVA in children.

Topics: Acetates; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Cough; Cyclopropanes; Fluticasone; Humans; Quinolines

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans

Fluticasone propionate/formoterol fumarate (FP/FORM) is one of the newer combinations among inhaled corticosteroid (ICS) and long-acting β2-agonist (LABA) combination formulations currently available. To evaluate the efficacy and safety of this FP/FORM combination, it is important to review all the available evidence and take a comprehensive look at the current and relevant data in the patient population suffering from asthma and chronic obstructive pulmonary disease (COPD).. In this focused review, we summarize the available literature published until January 2021 using the PubMed/Medline and Cochrane Controlled Trials Register databases on the efficacy and safety of FP/FORM with its mono-components; concurrent administration of FP+FORM; and with other ICS/LABA combinations in asthma and COPD patients.. FP/FORM combination therapy is a strong alternative in the treatment of persistent asthma and moderate-severe COPD. Extensive study of several trials has established the superior efficacy of FP/FORM combination therapy over FP or FORM monotherapy, comparable efficacy with FP+FORM and non-inferiority to other ICS/LABA fixed-dose combinations. The safety profile of FP/FORM has also been found to be comparable with respect to its mono-components and their concurrent use, and also other ICS/LABA combinations such as formoterol/budesonide and fluticasone/salmeterol.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Drug Combinations; Fluticasone; Formoterol Fumarate; Humans; Propionates; Pulmonary Disease, Chronic Obstructive

Inhaled corticosteroids (ICSs) have been widely used in chronic airway diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis. However, whether ICS use causes mycobacterial infection is uncertain. Some conclusions of published studies were inconsistent.. We aimed to investigate the association between the use of ICSs and mycobacterial infections in patients with chronic airway diseases.. This review was registered on PROSPERO (CRD42021284607). We focused on examining the association between ICS use and mycobacterial infection (nontuberculous mycobacterial [NTM] infection as well as tuberculosis [TB]). We searched PubMed (MEDLINE), Sciencenet, Cochrane, and EMBASE databases for studies up to 2021 to retrieve articles. The enrollment conditions included gender, enrollment diagnosis and ICS use in chronic airway disease patients, and so on. Preclinical studies, review articles, editorials, reviews, conference abstracts, and book chapters were excluded. Methodologically, the study was assessed using the Newcastle Ottawa Scale, and Rev-man5 was used for statistical analysis.. Ten studies (including 4 NTM and 6 TB articles) with 517,556 patients met the inclusion criteria and were included in this meta-analysis. From the NTM pooled analyses, ICS use was associated with increased odds of NTM infection in patients with chronic airway diseases (odds ratio [OR] = 3.93, 95% confidence interval [CI] 2.12-7.27), subgroup analysis showed that high-dose ICS use (OR = 2.27, 95% CI 2.08-2.48) and fluticasone use (OR = 2.42, 95% CI 2.23-2.63) were associated with increased odds of NTM infection risk in patients with chronic respiratory diseases. The TB pooled analyses showed a significant association between ICS use and risk of TB infection in patients with chronic respiratory diseases (OR = 2.01, 95% CI 1.23-3.29). Subgroup analysis showed that in chronic respiratory diseases, ICS use increased odds of TB infection in high-dose ICS use (OR = 1.70, 95% CI 1.56-1.86) and in COPD patients (OR = 1.45, 95% CI 1.29-1.63).. Our meta-analysis indicated that ICS use may increase the odds of mycobacterial infection in chronic respiratory disease patients, and this conclusion is more applicable to patients with high dose of ICS or fluticasone in NTM infection subgroups. In addition, high-dose ICS use may have higher risk of TB infection in patients with chronic respiratory diseases, especially COPD. Therefore, we should be vigilant about the application of ICS use in chronic respiratory diseases to avoid infection.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Fluticasone; Humans; Mycobacterium Infections, Nontuberculous; Pulmonary Disease, Chronic Obstructive; Tuberculosis

The claimed functional basis for ICSs in asthma and COPD is airway selectivity, attained by inhaling a potent, lipophilic compound with long local dissolution/absorption time. The development has been empirically based, resulting in five widely used ICSs. Among them, budesonide (BUD) deviates by being less lipophilic, leading to a more rapid systemic uptake with plasma peaks with some systemic anti-inflammatory activity. By this, BUD fits less well into the current pharmacological dogma of optimal ICS profile. In this review we compared the physicochemical, pharmacological and clinical properties of BUD, fluticasone propionate (FP) and fluticasone furoate (FF), representing different levels of lipophilicity, airway and systemic kinetics, focusing on their long-acting β2-agonist (LABA) combinations, in line with current GINA and GOLD recommendations. We are aware of the differences between formoterol (FORM) and the not rapid acting LABAs such as e.g. salmeterol and vilanterol but our comparisons are based on currently available combination products. A beclomethasone dipropionate (BDP)/FORM combination is also commented upon. Based on clinical comparisons in asthma and COPD, we conclude that the BUD/formoterol (BUD/FORM) combination is as effective and safe as the FP and FF combinations, and is in some cases even better as it can be used as "maintenance plus reliever therapy" (MART) in asthma and as maintenance in COPD. This is difficult to explain by current views of required ICS's/LABAs pharmacokinetic profiles. We propose that BUD achieves its efficacy by a combination of airway and systemic activity. The airway activity is dominating. The systemic activity contributes by plasma peaks, which are high enough for supportive anti-inflammatory actions at the blood and bone marrow levels but not sufficiently long to trigger a similar level of systemic adverse effects. This may be due to BUD's capacity to exploit a systemic differentiation mechanism as programmed for cortisol's various actions. This differentiation prospect can be reached only for an ICS with short plasma half-life. Here we present an alternative mode for an ICS to reach combined efficacy and safety, based on a poorly investigated and exploited physiological mechanism. A preference of this mode is broader versatility, due to that its straighter dose-response should allow a better adaptation to disease fluctuations, and that its rapid activity enables use as "anti-inflammatory reliever".

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Fluticasone; Formoterol Fumarate; Humans; Pulmonary Disease, Chronic Obstructive

This network meta-analysis (NMA) compared fixed-dose, twice daily fluticasone propionate/salmeterol (FP/Sal) vs. inhaled corticosteroid (ICS) and other ICS/long-acting beta-agonists (LABA) treatments, including when administered using maintenance and reliever therapy (MART) regimens, in terms of improvements in health-related quality of life (HRQoL). The relationship between changes in asthma control and HRQoL was assessed.. Articles published between 2001 and 2021, reporting change from baseline (CFB) in Asthma Quality of Life Questionnaire (AQLQ) in patients with moderate-to-severe asthma, were identified by a systematic review. Random effects Bayesian NMAs derived estimates of the mean difference in CFB in AQLQ vs. other interventions connected to the network (included 15 studies). Sensitivity analyses explored the impacts of differences in follow-up duration, baseline asthma control, the inclusion of observational studies, adjusting for baseline FEV. Mean CFB in AQLQ with FP/Sal vs. comparators demonstrated expected ranked effects: mean difference 0.65 [95% credible interval: 0.54, 0.78] versus placebo, 0.58 [ 0.33, 0.84] versus LABA, 0.21 [ 0.13, 0.31] versus ICS alone, 0.06 [-0.04, 0.19] versus other ICS/LABA, and 0.00 [-0.13, 0.14] versus ICS/formoterol MART. Sensitivity analyses largely showed consistent results. Improvements in AQLQ and ACQ were strongly correlated (R = 0.94).. This NMA demonstrates that HRQoL is responsive to treatment, is strongly related to asthma control and that it can be well-managed in patients with moderate-to-severe asthma using regular treatment with inhaled FP/Sal.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Bayes Theorem; Bronchodilator Agents; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Network Meta-Analysis; Quality of Life

An inhaled corticosteroid (ICS)-long-acting beta-2 agonist (LABA) combination has become the standard of care in asthma. Various ICS-LABAs are commercially available providing the clinician with many choices. A thorough understanding of the clinical efficacy and safety of various formulations will immensely benefit the prescribing doctor to decide the choice of agent. The present systematic review was undertaken to compare the clinical efficacy and safety of formoterol fluticasone (FF) to other ICS/LABA combinations in asthmatics.. The review adhered to the general principles mentioned in the CRD guidance and the PRISMA statement. We searched Medline, Embase, and Cochrane Controlled Trials Register databases on the efficacy of FF in treating asthma compared with other ICS-LABAs. A total of 138 trials identified initially. Only trials comparing the efficacy and safety of FF in comparision with Salmeterol/fluticasone (SF) or Budesonide/Formoterol (BF) were selected. The outcomes compared were onset of bronchodilator action, improvement in lung function, asthma control, asthma-related quality of life and risk of pneumonia.. Sixteen studies were included in the final analysis. FF therapy provided faster onset of bronchodilatation than SF. A better improvement in lung function was seen with FF inhaler use as compared with comparators in two studies. Patients using the FF inhaler had a non-inferior asthma control and asthma-related quality of life. Pneumonia risk was least with FF usage.. FF provides faster onset of action, numerically superior improvement in lung function and comparable asthma control than other ICS-LABA formulations. FF has better safety evidenced by lower occurrence of pneumonia.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Androstadienes; Asthma; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Pneumonia; Quality of Life

Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma.. A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I2 ≥ 50%) or fixed-effects model (I2 < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible.. Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF)%pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57-9.34; I2 = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24-1.85; I2 = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39-3.21; I2 = 72%; P < 0.001) compared with MFC.. SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs.. CRD42019133156.

Topics: Acetates; Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Albuterol; Anti-Asthmatic Agents; Asthma; Child; Cyclopropanes; Drug Therapy, Combination; Fluticasone; Humans; Quinolines; Salmeterol Xinafoate; Sulfides

Candidiasis is a rare entity reported as an isolated and primary laryngeal disease. In this condition, inhaled steroids were the single most common predisposing factor. Also mycotic infections of larynx are frequently seen in patients with immune insufficiency, although they have also been reported in individual with normal immune status. We report a case of isolated laryngeal Candidiasis in an immunocompetent individual, with an unusual presentation with exophytic lesion, edema, ulceration, white plaque, and pseudomembranous formation mimicking supraglottic carcinoma, to highlight the clinical of this condition and provide a review of the literature.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Anti-Asthmatic Agents; Antifungal Agents; Asthma; Candidiasis; Diagnosis, Differential; Fluticasone; Humans; Laryngeal Diseases; Laryngeal Neoplasms; Laryngoscopy; Male; Pulmonary Disease, Chronic Obstructive; Risk Factors; Salmeterol Xinafoate

Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and bronchodilators can result in good control of symptoms, prevention of further morbidity, and improved quality of life. However, an increase in serious adverse events with the use of both regular formoterol and regular salmeterol (long-acting beta₂-agonists) compared with placebo for chronic asthma has been demonstrated in previous Cochrane Reviews. This increase was statistically significant in trials that did not randomise participants to an inhaled corticosteroid, but not when formoterol or salmeterol was combined with an inhaled corticosteroid. The confidence intervals were found to be too wide to ensure that the addition of an inhaled corticosteroid renders regular long-acting beta₂-agonists completely safe; few participants and insufficient serious adverse events in these trials precluded a definitive decision about the safety of combination treatments.. To assess risks of mortality and non-fatal serious adverse events in trials that have randomised patients with chronic asthma to regular formoterol and an inhaled corticosteroid versus regular salmeterol and an inhaled corticosteroid.. We searched the Cochrane Airways Register of Trials, CENTRAL, MEDLINE, Embase, and two trial registries to identify reports of randomised trials for inclusion. We checked manufacturers' websites and clinical trial registers for unpublished trial data, as well as Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was  24 February 2021.. We included controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma, if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid) and were of at least 12 weeks' duration.. Two review authors independently selected trials for inclusion in the review, extracted outcome data from published papers and trial registries, and applied GRADE rating for the results. We sought unpublished data on mortality and serious adverse events from study sponsors and authors. The primary outcomes were all cause mortality and non-fatal serious adverse events. We chose not to calculate an average result from all the formulations of formoterol and inhaled steroid, as the doses and delivery devices are too diverse to assume a single class effect.. Twenty-one studies in 11,572 adults and adolescents and two studies in 723 children met the eligibility criteria of the review. No data were available for two studies; therefore these were not included in the analysis. Among adult and adolescent studies, seven compared formoterol and budesonide to salmeterol and fluticasone (N = 7764), six compared formoterol and beclomethasone to salmeterol and fluticasone (N = 1923), two compared formoterol and mometasone to salmeterol and fluticasone (N = 1126), two compared formoterol and fluticasone to salmeterol and fluticasone (N = 790), and one compared formoterol and budesonide to salmeterol and budesonide (N = 229). In total, five deaths were reported among adults, none of which was thought to be related to asthma. The certainty of evidence for all-cause mortality was low, as there were not enough deaths to permit any precise conclusions regarding the risk of mortality on combination formoterol versus combination salmeterol. In all, 201 adults reported non-fatal serious adverse events. In studies comparing formoterol and budesonide to salmeterol and fluticasone, there were 77 in the formoterol arm and 68 in the salmeterol arm (Peto odds ratio (OR) 1.14, 95% confidence interval (CI) 0.82 to 1.59; 5935 participants, 7 studies; moderate-certainty evidence). In the formoterol and beclomethasone studies, there were 12 adults in the formoterol arm and 13 in the salmeterol arm with events (Peto OR 0.94, 95% CI 0.43 to 2.08; 1941 participants, 6 studies; moderate-certainty evidence). In the formoterol and mometasone studies, there were 18 in the formoterol arm and 11 in the salmeterol arm (Peto OR 1.02, 95% CI 0.47 to 2.20; 1126 participants, 2 studies; moderate-certainty evidence). One adult in the formoterol and fluticasone studies in the salmeterol arm experienced an event (Peto OR 0.05, 95% CI 0.00 to 3.10; 293 participants, 2 studies; low-certainty evidence). Another adult in the formoterol and budesonide compared to salmeterol and budesonide study in the formoterol arm had an event (Peto OR 7.45, 95% CI 0.15 to 375.68; 229 participants, 1 study; low-certainty evidence). Only 46 adults were reported to have experienced asthma-related serious adverse events. The certainty of the evidence was low to very low due to the small number of events and the absence of independent assessment of causation. The two studies in children compared formoterol and fluticasone to salmeterol and fluticasone. No deaths and no asthma-rel. Overall, for both adults and children, evidence is insufficient to show whether regular formoterol in combination with budesonide, beclomethasone, fluticasone, or mometasone has a different safety profile from salmeterol in combination with fluticasone or budesonide. Five deaths of any cause were reported across all studies and no deaths from asthma; this information is insufficient to permit any firm conclusions about the relative risks of mortality on combination formoterol in comparison to combination salmeterol inhalers. Evidence on all-cause non-fatal serious adverse events indicates that there is probably little to no difference between formoterol/budesonide and salmeterol/fluticasone inhalers. However events for the other formoterol combination inhalers were too few to allow conclusions. Only 46 non-fatal serious adverse events were thought to be asthma related; this small number in addition to the absence of independent outcome assessment means that we have very low confidence for this outcome. We found no evidence of safety issues that would affect the choice between salmeterol and formoterol combination inhalers used for regular maintenance therapy by adults and children with asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Drug Therapy, Combination; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Mometasone Furoate; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

A systematic review and meta-analysis was performed to investigate the effect of fluticasone + salmeterol and fluticasone alone in the treatment of pediatric asthma.. Studies meeting specific selection criteria were selected from online databases, including Pubmed, Embase, and the Cochrane Library. The quality of randomized controlled trials was assessed using the Cochrane Library. Weighted mean difference (WMD) and 95% CI were used to evaluate the effect size of continuous variables, while rate ratio (RR) and 95% CI were used for dichotomous variables.. A total of 11 studies, including 8272 pediatric asthma patients, were included in this meta-analysis. Among these, 4133 patients were in the salmeterol + fluticasone group. The changes in forced expiratory volume in 1 second in children with asthma in the salmeterol + fluticasone and fluticasone alone groups were significantly different (fixed effects model, WMD=3.26, 95% CI: 1.52-5.00, P=0.0002). Asthma exacerbation between two groups were significantly different (fixed effects model, RR=0.85, 95% CI: 0.73-0.98, Z=2.18, P=0.03). There was no difference in the incidence of adverse events between salmeterol + fluticasone and fluticasone alone in the treatment of pediatric asthma (P>0.05). When the control group was treated with double dose fluticasone, the difference of changes in FEV1 and asthma exacerbation in children with asthma between the two groups was not significant.. The efficacy of salmeterol + fluticasone is better than fluticasone alone, and the efficacy of salmeterol + fluticasone is equal to doubling the dose of fluticasone in the treatment of pediatric asthma.

Topics: Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Combinations; Fluticasone; Formoterol Fumarate; Humans; Salmeterol Xinafoate

The proportion of the efficacy of high-dose inhaled corticosteroids (ICS) in oral corticosteroid-dependent asthma that is due to systemic effects is uncertain. This study aimed to estimate the ICS dose-response relationship for oral corticosteroid-sparing effects in oral corticosteroid-dependent asthma, and to determine the proportion of oral corticosteroid-sparing effects due to their systemic effects, based on the comparative dose-response relationship of ICS. Systematic review and meta-analysis of randomised controlled trials reporting oral corticosteroid-sparing effects of high-dose ICS in oral corticosteroid-dependent asthma. In addition, reports of oral corticosteroid to ICS dose-equivalence in terms of adrenal suppression were retrieved. The primary outcome was the proportion of the oral corticosteroid-sparing effect of ICS that could be attributed to systemic absorption, per 1000 µg increase of ICS, expressed as a ratio. This ratio estimates the oral corticosteroid sparing effect of ICS due to systemic effects.. 11 studies including 1283 participants reporting oral corticosteroid-sparing effects of ICS were identified. The prednisone dose decrease per 1000 µg increase in ICS varied from 2.1 mg to 4.9 mg, depending on the type of ICS. The ratio of the prednisone-sparing effect due to the systemic effects per 1000 µg of fluticasone propionate was 1.02 (95% CI 0.68-2.08) and for budesonide was 0.93 (95% CI 0.63-1.89).. In patients with oral corticosteroid-dependent asthma, the limited available evidence suggests that the majority of the oral corticosteroid-sparing effect of high-dose ICS is likely to be due to systemic effects.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Fluticasone; Humans

Some drugs can only be dispensed in multiple-dose containers. Multiple-dose packaging may pose a problem for hospitals in terms of drug wastage and cost. Oral inhalers, such as fluticasone propionate and salmeterol combination inhalers, are only available as multiple-dose formats in Canada.. The objectives of this study are to quantify the amount of fluticasone propionate and salmeterol combination inhaler waste and to assess possible factors that could be contributing to waste.. A retrospective chart review of 189 patients was conducted. Patients were included if they had received an order for fluticasone propionate and salmeterol combination inhaler at one of the 12 acute hospital sites of Fraser Health Authority. The primary outcome was the proportion of patients who were dispensed one or more inhalers unnecessarily. The number of inhalers dispensed was compared with the number of inhalers needed to complete a patient's order duration. The chart was also reviewed for possible factors that could have contributed to extra inhalers being dispensed unnecessarily.. Thirty-seven patients (19.6%) had at least one inhaler dispensed unnecessarily and thus wasted. About 17.4% of the total amount of inhalers dispensed were dispensed unnecessarily, and 76.3% of doses dispensed were wasted. The cost of inhalers wasted for our sample was $5151.12 (CAD). The most common factors that contributed to inhaler waste appeared to be loss of medication during patient transfers and storage of inhalers as wardstock.. The use of drugs that are only available in multiple-dose formats results in significant drug wastage and unnecessary health care expenditure. To minimize wastage of drug product, procedures could be implemented to ensure that drugs are properly transferred with the patient when a patient transfers locations in the hospital. As well, a review of wardstock inventory may minimize waste. Further assessment of multiple-dose drug product waste and evaluations of methods to mitigate waste are encouraged.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Canada; Drug Combinations; Fluticasone; Humans; Nebulizers and Vaporizers; Retrospective Studies; Salmeterol Xinafoate

Asthma is the commonest chronic disease affecting airways in humans and has an increasing global disease burden. Inhaled corticosteroids (ICS) are the first-line therapeutic option for asthma, and addition of a long-acting beta 2-agonist (LABA) has been shown to improve asthma control. A combination of the two agents in a single inhaler is beneficial with regard to ease of administration and patient compliance. Various ICS-LABA formulations are available across various countries in the world, one among them being formoterol-fluticasone. Both formoterol and fluticasone have pharmacologic peculiarities which places the combination in a uniquely advantageous position when it comes to asthma therapy. The present review focuses on some of the, hitherto, less explored aspects of this combination inhaler such as real-world efficacy, impact on budget allocation, results of switch-over therapy, and potential to improve adherence to asthma treatment. It also provides practical recommendations on positioning it in real-world asthma management.

Topics: Anti-Asthmatic Agents; Asthma; Drug Combinations; Fluticasone; Formoterol Fumarate; Health Expenditures; Humans; India; Medication Adherence; Nebulizers and Vaporizers; Patient Satisfaction; Treatment Outcome

Topics: Administration, Inhalation; Adolescent; Asthma; Beclomethasone; Body Height; Budesonide; Child; Child Development; Child, Preschool; Fluticasone; Glucocorticoids; Humans; Infant; Mometasone Furoate; Pregnenediones

The Global Initiative for Asthma guidelines use the traditional terminology of "low," "medium," and "high" doses of inhaled corticosteroids (ICS) to define daily maintenance doses of 100 to 250 μg, >250 to 500 μg, and >500 μg, respectively, of fluticasone propionate or equivalent for adults with asthma. This concise clinical review proposes that this terminology is not evidence based and that prescribing practice based on this terminology may lead to the use of inappropriately excessive doses of ICS. Specifically, the ICS dose that achieves 80-90% of the maximum obtainable benefit is currently classified as a low dose, with the description of two higher dose levels of medium and high, which are associated with significant risk of systemic adverse effects. Asthma guidelines and clinician prescribing practice need to be modified in accordance with the currently available evidence of the dose-response relationship of ICS in adult asthma. We propose a reclassification of ICS doses based on a "standard daily dose," which is defined as 200-250 μg of fluticasone propionate or equivalent, representing the dose at which approximately 80-90% of the maximum achievable therapeutic benefit of ICS is obtained in adult asthma across the spectrum of severity. It is recommended that ICS treatment be started at these standard doses, which then represent the doses at which maintenance ICS are prescribed at step 2 and within ICS/long-acting β-agonist combination therapy at step 3. The opportunity is available to prescribe higher doses within ICS/long-acting β-agonist maintenance therapy in accordance with the stepwise approach to asthma treatment at step 4.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; Male; Middle Aged; Practice Guidelines as Topic

Inhaled corticosteroids (ICS) are the most effective treatment for children with persistent asthma. Although treatment with ICS is generally considered to be safe in children, the potential adverse effects of these drugs on growth remains a matter of concern for parents and physicians.. To assess the impact of different inhaled corticosteroid drugs and delivery devices on the linear growth of children with persistent asthma.. We searched the Cochrane Airways Trials Register, which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, Embase, CINAHL, AMED and PsycINFO. We handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases, or contacted the manufacturer, to search for potential relevant unpublished studies. The literature search was initially conducted in September 2014, and updated in November 2015, September 2018, and April 2019.. We selected parallel-group randomized controlled trials of at least three months' duration. To be included, trials had to compare linear growth between different inhaled corticosteroid molecules at equivalent doses, delivered by the same type of device, or between different devices used to deliver the same inhaled corticosteroid molecule at the same dose, in children up to 18 years of age with persistent asthma.. At least two review authors independently selected studies and assessed risk of bias in included studies. The data were extracted by one author and checked by another. The primary outcome was linear growth velocity. We conducted meta-analyses using Review Manager 5.3 software. We used mean differences (MDs) and 95% confidence intervals (CIs ) as the metrics for treatment effects, and the random-effects model for meta-analyses. We did not perform planned subgroup analyses due to there being too few included trials.. We included six randomized trials involving 1199 children aged from 4 to 12 years (per-protocol population: 1008), with mild-to-moderate persistent asthma. Two trials were from single hospitals, and the remaining four trials were multicentre studies. The duration of trials varied from six to 20 months.One trial with 23 participants compared fluticasone with beclomethasone, and showed that fluticasone given at an equivalent dose was associated with a significant greater linear growth velocity (MD 0.81 cm/year, 95% CI 0.46 to 1.16, low certainty evidence). Three trials compared fluticasone with budesonide. Fluticasone given at an equivalent dose had a less suppressive effect than budesonide on growth, as measured by change in height over a period from 20 weeks to 12 months (MD 0.97 cm, 95% CI 0.62 to 1.32; 2 trials, 359 participants; moderate certainty evidence). However, we observed no significant difference in linear growth velocity between fluticasone and budesonide at equivalent doses (MD 0.39 cm/year, 95% CI -0.94 to 1.73; 2 trials, 236 participants; very low certainty evidence).Two trials compared inhalation devices. One trial with 212 participants revealed a comparable linear growth velocity between beclomethasone administered via hydrofluoroalkane-metered dose inhaler (HFA-MDI) and beclomethasone administered via chlorofluorocarbon-metered dose inhaler (CFC-MDI) at an equivalent dose (MD -0.44 cm/year, 95% CI -1.00 to 0.12; low certainty evidence). Another trial with 229 participants showed a small but statistically significant greater increase in height over a period of six months in favour of budesonide via Easyhaler, compared to budesonide given at the same dose via Turbuhaler (MD 0.37 cm, 95% CI 0.12 to 0.62; low certainty evidence).. This review suggests that the drug molecule and delivery device may impact the effect size of ICS on growth in children with persistent asthma. Fluticasone at an equivalent dose seems to inhibit growth less than beclomethasone and budesonide. Easyhaler is likely to have less adverse effect on growth than Turbuhaler when used for delivery of budesonide. However, the evidence from this systematic review of head-to-head trials is not certain enough to inform the selection of inhaled corticosteroid or inhalation device for the treatment of children with persistent asthma. Further studies are needed, and pragmatic trials and real-life observational studies seem more attractive and feasible.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Beclomethasone; Body Height; Budesonide; Child; Child, Preschool; Fluticasone; Growth; Humans; Metered Dose Inhalers; Randomized Controlled Trials as Topic; Time Factors

Adverse events (AEs) associated with short-term corticosteroid use for respiratory conditions in young children.. Systematic review of primary studies.. Medline, Cochrane CENTRAL, Embase and regulatory agencies were searched September 2014; search was updated in 2017.. Children <6 years with acute respiratory condition, given inhaled (high-dose) or systemic corticosteroids up to 14 days.. One reviewer extracted with another reviewer verifying data. Study selection and methodological quality (McHarm scale) involved duplicate independent reviews. We extracted AEs reported by study authors and used a categorisation model by organ systems. Meta-analyses used Peto ORs (pORs) and DerSimonian Laird inverse variance method utilising Mantel-Haenszel Q statistic, with 95% CI. Subgroup analyses were conducted for respiratory condition and dose.. Eighty-five studies (11 505 children) were included; 68 were randomised trials. Methodological quality was poor overall due to lack of assessment and inadequate reporting of AEs. Meta-analysis (six studies; n=1373) found fewer cases of vomiting comparing oral dexamethasone with prednisone (pOR 0.29, 95% CI 0.17 to 0.48; I. Evidence suggests that short-term high-dose inhaled or systemic corticosteroids use is not associated with an increase in AEs across organ systems. Uncertainties remain, particularly for recurrent use and growth outcomes, due to low study quality, poor reporting and imprecision.

Topics: Acute Disease; Administration, Inhalation; Administration, Intravenous; Administration, Oral; Adrenal Cortex Hormones; Asthma; Bronchiolitis, Viral; Child, Preschool; Croup; Dexamethasone; Fluticasone; Glucocorticoids; Growth Disorders; Headache; Humans; Infant; Injections, Intramuscular; Pneumonia; Prednisone; Respiratory Sounds; Respiratory Tract Diseases; Respiratory Tract Infections; Tremor; Vomiting

Many trials have been published comparing inhaled corticosteroid (ICS) treatments in asthma. However, mixed results necessitate the summarization of available evidence to aid in decision-making. Areas covered: This systematic review evaluated randomized controlled trials (RCTs) that compared the efficacy and safety of inhaled fluticasone propionate (FP) with other ICS including beclomethasone dipropionate (BDP), budesonide (BUD) and ciclesonide (CIC). PubMed was searched and 54 RCTs that fit pre-determined criteria were included. Endpoints evaluated included lung function, asthma symptom control, exacerbation frequency, reliever use, quality of life and steroid-related side effects. Expert commentary: Across all studies, FP was associated with either more favorable or at least similar efficacy and safety, in comparison with BDP or BUD. This observation may be related to FP's higher relative potency and almost negligible oral bioavailability. FP was comparable to CIC for efficacy. However, CIC appeared to have a smaller impact on cortisol levels than FP, which is likely due to CIC's incomplete conversion to active metabolite (des-CIC) and the lower potency of des-CIC compared with FP. Although there were no significant differences in evaluated outcomes after treatment with different ICS in the majority of studies, some observed differences could be explained by their respective pharmacodynamic and pharmacokinetic properties.

Topics: Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Fluticasone; Glucocorticoids; Humans; Nebulizers and Vaporizers; Pregnenediones; Randomized Controlled Trials as Topic

Fluticasone furoate and fluticasone propionate are recommended options for prophylactic maintenance treatment of persistent asthma. Using data from two previous clinical studies (GSK studies: FFA109685/NCT00603278, FFA112059/NCT01159912), this meta-analysis compared change from baseline in clinic visit mean trough forced expiratory volume in 1 s (FEV

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Asthma; Bronchodilator Agents; Drug Administration Schedule; Fluticasone; Forced Expiratory Volume; Humans; Treatment Outcome

In the treatment of chronic obstructive pulmonary disease (COPD), bronchodilators such as long acting muscarinic antagonist (LAMA) and long acting β agonist(LABA) play key roles for improving respiratory function and symptoms, and reducing risk of exacerbation. However, inhaled corticosteroid (ICS), a key medicine for bronchial asthma, is limitedly used in COPD treatment. Japanese Respiratory Society recommends to use ICS for severe COPD patients who have been frequently exacerbated, because previous clinical studies indicated that ICS reduces exacerbation in moderate to severe COPD patients. Asthma sometimes overlaps with COPD, and symptoms of those patients are not well controlled by the bronchodilation therapy alone. Therefore, ICS/LABA or ICS/LAMA should be prescribed to those overlapped patients. Concentration of exhaled nitrogen oxide and percentage of peripheral eosinophil may be good biomarkers for discriminating the COPD patients who have good response to ICS treatment.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Asthma; Biomarkers; Breath Tests; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Delayed-Action Preparations; Disease Progression; Drug Combinations; Drug Therapy, Combination; Eosinophils; Fluticasone; Glucocorticoids; Humans; Leukocyte Count; Muscarinic Antagonists; Nitrogen Oxides; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Severity of Illness Index; Tiotropium Bromide

The fixed-dose combination fluticasone propionate/formoterol (FPF) is a novel combination of a widely known and used inhaled glucocorticoid (IGC) and a long-acting β2-adrenergic agonist (LABA), available for the first time in a single device. This fixed-dose combination of FPF has a demonstrated efficacy and safety profile in clinical trials compared with its individual components and other fixed-dose combinations of IGC/LABA and is indicated for the treatment of persistent asthma in adults and adolescents. FPF is available in a wide range of doses that can adequately cover the therapeutic steps recommended by treatment guidelines, constituting a fixed-dose combination of GCI/LABA that is effective, rapid, well tolerated and with a reasonable acquisition cost. Various assessment agencies of the Spanish Autonomous Communities consider this combination to be an appropriate alternative therapy for asthma in the primary care setting.

Topics: Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Dose-Response Relationship, Drug; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Practice Guidelines as Topic; Primary Health Care; Spain

Orally inhaled agents are a key therapeutic class for treatment of asthma. Inhaled corticosteroids (ICS) are the most effective anti-inflammatory treatment for asthma thus representing the first-line therapy and bronchodilators complement the effects of ICSs. A significant body of evidence indicates that addition of a β2-agonist to ICS therapy is more effective than increasing the dose of ICS monotherapy. In this paper, pharmacological features of available ICSs and bronchodilators will be reviewed with a focus on fluticasone propionate/formoterol fumarate combination which represents the one of the most powerful ICS acting together with the most rapid active LABA.

Topics: Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans

The major influencing factors on persistent asthma control are the selected treatment(s), the drug delivery route and patient's adherence to therapy, together with the influence of lifestyle (i.e. sedentary habit), comorbid conditions and specific asthma phenotypes. Inhaled corticosteroids (ICS) in combination with a long-acting β2-agonist (LABA) are the gold standard for management of persistent asthma, with maximal local targeting and minimal systemic side effects. Several innovative inhaler devices have been developed for effective local drug administration and good patient compliance to therapy. Recently, a new ICS/LABA fixed combination, formulated with fluticasone propionate (FP) and formoterol fumarate (FF), has been proposed for maintenance treatment of asthma in adults and adolescent patients. FP/FF combines the anti-inflammatory and bronchodilating properties of powerful compounds in a single inhaler. Its pharmacological characteristics allow rapid speed of onset and dosage flexibility required for step-up and step-down strategies, improving adherence to treatment of asthmatic patients. The efficacy of the FP/FF fixed combination at all dosages in controlling asthma symptoms and the reduced rate of discontinuation have been demonstrated by all randomized trials conducted so far.

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Drug Combinations; Fluticasone; Formoterol Fumarate; Humans; Medication Adherence

A good level of asthma control improves the quality of life of asthmatic patients and may prevent future risk in term of exacerbations and decline of pulmonary function. However, in a real-life setting, several factors contribute to generally low compliance to the treatment. A rapid-onset, long-lasting medication with few adverse effects may contribute to improve adherence to therapy, along with an effective patient education and a good physician-patient communication. Many clinical studies demonstrated the comparable efficacy of the new fluticasone propionate/formoterol (FP/F) combination in a single inhaler to other combinations of inhaled corticosteroids and β2agonists and the superiority of FP/F as compared to its individual components. Also the safety profile of this combination was encouraging in all studies, even at higher doses. By effectively and safely targeting both airway inflammation and smooth muscle dysfunction, the two pathological facets of asthma, and allowing the patient to adapt dose strength, FP/F combination in a single device represents a valid option to improve asthma control in patients with different levels of asthma severity.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Drug Combinations; Fluticasone; Formoterol Fumarate; Humans; Medication Adherence; Nebulizers and Vaporizers; Patient Education as Topic; Quality of Life

Treatment guidelines for asthma recommend inhaled corticosteroids (ICS) as first-line therapy for children with persistent asthma. Although ICS treatment is generally considered safe in children, the potential systemic adverse effects related to regular use of these drugs have been and continue to be a matter of concern, especially the effects on linear growth.. To assess the impact of ICS on the linear growth of children with persistent asthma and to explore potential effect modifiers such as characteristics of available treatments (molecule, dose, length of exposure, inhalation device) and of treated children (age, disease severity, compliance with treatment).. We searched the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, EMBASE, CINAHL, AMED and PsycINFO; we handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases to look for potential relevant unpublished studies. The literature search was conducted in January 2014.. Parallel-group randomised controlled trials comparing daily use of ICS, delivered by any type of inhalation device for at least three months, versus placebo or non-steroidal drugs in children up to 18 years of age with persistent asthma.. Two review authors independently performed study selection, data extraction and assessment of risk of bias in included studies. We conducted meta-analyses using the Cochrane statistical package RevMan 5.2 and Stata version 11.0. We used the random-effects model for meta-analyses. We used mean differences (MDs) and 95% CIs as the metrics for treatment effects. A negative value for MD indicates that ICS have suppressive effects on linear growth compared with controls. We performed a priori planned subgroup analyses to explore potential effect modifiers, such as ICS molecule, daily dose, inhalation device and age of the treated child.. We included 25 trials involving 8471 (5128 ICS-treated and 3343 control) children with mild to moderate persistent asthma. Six molecules (beclomethasone dipropionate, budesonide, ciclesonide, flunisolide, fluticasone propionate and mometasone furoate) [corrected] given at low or medium daily doses were used during a period of three months to four to six years. Most trials were blinded and over half of the trials had drop out rates of over 20%.Compared with placebo or non-steroidal drugs, ICS produced a statistically significant reduction in linear growth velocity (14 trials with 5717 participants, MD -0.48 cm/y, 95% CI -0.65 to -0.30, moderate quality evidence) and in the change from baseline in height (15 trials with 3275 participants; MD -0.61 cm/y, 95% CI -0.83 to -0.38, moderate quality evidence) during a one-year treatment period.Subgroup analysis showed a statistically significant group difference between six molecules in the mean reduction of linear growth velocity during one-year treatment (Chi² = 26.1, degrees of freedom (df) = 5, P value < 0.0001). The group difference persisted even when analysis was restricted to the trials using doses equivalent to 200 μg/d hydrofluoroalkane (HFA)-beclomethasone. Subgroup analyses did not show a statistically significant impact of daily dose (low vs medium), inhalation device or participant age on the magnitude of ICS-induced suppression of linear growth velocity during a one-year treatment period. However, head-to-head comparisons are needed to assess the effects of different drug molecules, dose, inhalation device or patient age. No statistically significant difference in linear growth velocity was found between participants treated with ICS and controls during the second year of treatment (five trials with 3174 participants; MD -0.19 cm/y, 95% CI -0.48 to 0.11, P value 0.22). Of two trials that reported linear growth velocity in the third year of treatment, one trial involving 667 participants showed similar growth velocity between the budesonide and placebo groups (5.34 cm/y vs 5.34 cm/y), and another trial involving 1974 participants showed lower growth velocity in the budesonide group compared with the placebo group (MD -0.33 cm/y, 95% CI -0.52 to -0.14, P value 0.0005). Among four trials reporting data on linear growth after treatment cessation, three did not describe statistically significant catch-up growth in the ICS group two to four months after treatment cessation. One trial showed accelerated li. Regular use of ICS at low or medium daily doses is associated with a mean reduction of 0.48 cm/y in linear growth velocity and a 0.61-cm change from baseline in height during a one-year treatment period in children with mild to moderate persistent asthma. The effect size of ICS on linear growth velocity appears to be associated more strongly with the ICS molecule than with the device or dose (low to medium dose range). ICS-induced growth suppression seems to be maximal during the first year of therapy and less pronounced in subsequent years of treatment. However, additional studies are needed to better characterise the molecule dependency of growth suppression, particularly with newer molecules (mometasone, ciclesonide), to specify the respective role of molecule, daily dose, inhalation device and patient age on the effect size of ICS, and to define the growth suppression effect of ICS treatment over a period of several years in children with persistent asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Child, Preschool; Fluocinolone Acetonide; Fluticasone; Growth; Growth Disorders; Humans; Mometasone Furoate; Patient Dropouts; Pregnadienediols; Pregnenediones

Inhaled corticosteroids (ICS) are the first-line treatment for children with persistent asthma. Their potential for growth suppression remains a matter of concern for parents and physicians.. To assess whether increasing the dose of ICS is associated with slower linear growth, weight gain and skeletal maturation in children with asthma.. We searched the Cochrane Airways Group Specialised Register of trials (CAGR) and the ClinicalTrials.gov website up to March 2014.. Studies were eligible if they were parallel-group randomised trials evaluating the impact of different doses of the same ICS using the same device in both groups for a minimum of three months in children one to 17 years of age with persistent asthma.. Two review authors ascertained methodological quality independently using the Cochrane Risk of bias tool. The primary outcome was linear growth velocity. Secondary outcomes included change over time in growth velocity, height, weight, body mass index and skeletal maturation.. Among 22 eligible trials, 17 group comparisons were derived from 10 trials (3394 children with mild to moderate asthma), measured growth and contributed data to the meta-analysis. Trials used ICS (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) as monotherapy or as combination therapy with a long-acting beta2-agonist and generally compared low (50 to 100 μg) versus low to medium (200 μg) doses of hydrofluoroalkane (HFA)-beclomethasone equivalent over 12 to 52 weeks. In the four comparisons reporting linear growth over 12 months, a significant group difference was observed, clearly indicating lower growth velocity in the higher ICS dose group of 5.74 cm/y compared with 5.94 cm/y on lower-dose ICS (N = 728 school-aged children; mean difference (MD)0.20 cm/y, 95% confidence interval (CI) 0.02 to 0.39; high-quality evidence): No statistically significant heterogeneity was noted between trials contributing data. The ICS molecules (ciclesonide, fluticasone, mometasone) used in these four comparisons did not significantly influence the magnitude of effect (X(2) = 2.19 (2 df), P value 0.33). Subgroup analyses on age, baseline severity of airway obstruction, ICS dose and concomitant use of non-steroidal antiasthmatic drugs were not performed because of similarity across trials or inadequate reporting. A statistically significant group difference was noted in unadjusted change in height from zero to three months (nine comparisons; N = 944 children; MD 0.15, 95% CI -0.28 to -0.02; moderate-quality evidence) in favour of a higher ICS dose. No statistically significant group differences in change in height were observed at other time points, nor were such differences in weight, bone mass index and skeletal maturation reported with low quality of evidence due to imprecision.. In prepubescent school-aged children with mild to moderate persistent asthma, a small but statistically significant group difference in growth velocity was observed between low doses of ICS and low to medium doses of HFA-beclomethasone equivalent, favouring the use of low-dose ICS. No apparent difference in the magnitude of effect was associated with three molecules reporting one-year growth velocity, namely, mometasone, ciclesonide and fluticasone. In view of prevailing parents' and physicians' concerns about the growth suppressive effect of ICS, lack of or incomplete reporting of growth velocity in more than 86% (19/22) of eligible paediatric trials, including those using beclomethasone and budesonide, is a matter of concern. All future paediatric trials comparing different doses of ICS with or without placebo should systematically document growth. Findings support use of the minimal effective ICS dose in children with asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Dose-Response Relationship, Drug; Fluticasone; Growth; Growth Disorders; Humans; Mometasone Furoate; Pregnadienediols; Pregnenediones; Randomized Controlled Trials as Topic

International guidelines describe asthma control as the main outcome of asthma management. Prevention of symptoms, improved quality of life, and reduction of exacerbations are the main components, consequently decreasing health care costs. However, many of these objectives remain unmet in real life: several surveys show that a large proportion of asthmatic patients are not well controlled despite the efficacy of current available treatment. Several randomized controlled clinical trials indicate that combining inhaled corticosteroids and long-acting β2-agonists, by means of a single inhaler, greatly improves the management of the disease. The results of 9 multicenter phase III clinical studies demonstrate that the fixed combination of fluticasone propionate/formoterol in a single inhaler is effective in terms of lung function and symptom control. These studies highlight the dose flexibility, safety and tolerability of this new inhaled combination. These characteristics meet the recommendations of international guidelines, and the preferences of respiratory physicians who identified these aspects as critical components of a successful asthma therapy. Combination of fluticasone propionate/formoterol in a single inhaler provides potent anti-inflammatory activity of fluticasone propionate and rapid onset of action of the β2-agonist formoterol making this association a viable treatment option both in terms of effectiveness and compliance.

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Drug Combinations; Ethanolamines; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Particle Size; Quality of Life; Treatment Outcome

To evaluate the cost-utility of the treatment with a long acting beta-agonist (LABA) and inhaled corticosteroid (ICS) combination inhaler [salmeterol xinafoate (SAL)/fluticasone propionate (FP) combination inhaler (SFC) (Advair(®))] to continuing on current ICS dose (no ICS dose change) or increased ICS dose [fluticasone propionate (FP)] in patients with uncontrolled asthma in Canada.. A cost-utility analysis was conducted from a Canadian public healthcare perspective with a one year time horizon. In the no FP dose change scenarios, remaining on daily low (FP 100 ug BID) or medium (FP 200-250 ug BID) or high dose (FP 500 ug BID) was considered. In the increased FP dose scenarios, doubling the FP dose from low to medium dose and from medium to high dose regimens were considered. A decision model was developed with two health states: "symptom free" or "with symptoms". Clinical efficacy was based on a meta-analysis of relevant randomized controlled trials. Over the one year time horizon the percentage with symptom free days (SFD) was used as the measure of differential treatment scenario effectiveness. Drug costs and non-drug costs were incorporated into the analysis. Utilities, derived from EQ5D scores and health services resource use based on patient diaries for 'symptom free' and 'with symptoms' were based on regression analyses of individual patient data from the Gaining Optimal Asthma controL (GOAL) trial. Costs were assessed by assigning unit cost for each health services resource use for each patient. The incremental cost-utility ratios (ICUR) for SFC vs no FP dose change or increased FP dose were estimated using descriptive statistics. Uncertainty was assessed by deterministic and probabilistic sensitivity analysis (PSA).. Over one year, SFC resulted in an incremental cost per patient of $544-$655 compared to no FP dose change and $47-$380 per year compared to increased FP dose. SFC results in incremental QALYs per patient of 0.0100-0.0149 compared to no FP dose change and 0.0136-0.0152 compared to increased FP dose. The one year ICURs were $43,000 to $54,400 per QALY gained for SFC compared to no FP dose change and $25,000 to $3500 per QALY gained compared to increased FP dose scenarios. The probability of SFC being cost-effective at $50,000 per QALY gained was greater than 75% compared to increased FP dose scenarios and compared to no dose change for patients on low or medium dose FP. The results were robust to changes in assumptions within the model.. In Canadian patients with inadequately controlled asthma on FP, it is cost-effective to use SFC for patients 12 years and over compared to doubling their FP dose. It is also cost-effective to use SFC for patients on low or medium dose FP compared to remaining on the current FP dose in patients with uncontrolled asthma.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Canada; Child; Cost-Benefit Analysis; Decision Support Techniques; Dose-Response Relationship, Drug; Drug Combinations; Drug Costs; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Health Care Costs; Humans; Male; Middle Aged; Quality-Adjusted Life Years; Treatment Outcome; Young Adult

Pharmacologic treatment of asthma should be done with a stepwise approach recommended in treatment guidelines. If inhaled corticosteroids (ICSs) alone are not adequate, ICSs in combination with long-acting β-agonists (LABAs) are now established and widely used as the next step in effective controller therapy. Fixed-dose ICS/LABA combinations in a single device are the preferred form of delivery and improve compliance by enabling patients to get symptom relief from the LABA while receiving the anti-inflammatory benefits of ICSs. Fluticasone propionate/formoterol fumarate is one of the newest fixed-dose combinations. It has been in use in Europe in 2012, but is still under regulatory review in the US. Fluticasone is a synthetic ICS with potent anti-inflammatory effects, while formoterol is a selective β2-adrenergic receptor agonist with a rapid onset of bronchodilation within 5-10 minutes and a 12-hour duration of action. Fluticasone/formoterol has shown superior efficacy when compared to fluticasone or formoterol alone in multiple well-designed studies. The combination has shown comparable or "noninferior" benefits in lung function, clinical symptoms, and asthma control when compared with fluticasone and formoterol administered concurrently in separate inhalers. Fluticasone/formoterol provides similar efficacy with fluticasone/salmeterol, but with more rapid symptom relief. It has been compared directly with budesonide/formoterol with comparable results. Fluticasone/formoterol is well tolerated, with no unusual or increased safety concerns versus each individual component or other available ICS/LABA combinations. Fluticasone/formoterol is the latest entry into a relatively crowded market of branded fixed-dose preparations. Upcoming generic fixed-dose combinations and once-daily agents pose significant market challenges. In clinical practice, most practitioners consider all the currently available fixed-dose preparations to be of comparable efficacy and safety.

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Dose-Response Relationship, Drug; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Safety

The combination of an inhaled corticosteroid and a long acting beta-2 agonist is indicated for the regular treatment of persistent moderate-to-severe asthmatics whose asthma is not controlled by inhaled corticosteroids and the occasional use of a short acting beta-2 agonist. The aim of this review is to give an overview of the rationale of combining formoterol and fluticasone and to analyze the clinical data concerning a new fixed combination of fluticasone and formoterol in a pressurised metered-dose inhaler with a dose counter (Flutiform(®)) that was approved for the treatment of asthma in France in 2013. The clinical studies provide evidence that combined fluticasone/formoterol is more efficacious than fluticasone or formoterol given alone, and provides similar improvements in lung function to fluticasone (Flixotide(®)) and formoterol (Foradil(®)) administered concurrently. The combination of fluticasone/formoterol gave a more rapid bronchodilatation than the combination fluticasone/salmeterol. As a whole, the combination of fluticasone/formoterol had similar efficacy and tolerability profiles to the combinations of either budesonide/formoterol or fluticasone/salmeterol.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Combinations; Ethanolamines; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Metered Dose Inhalers

Inhaled corticosteroids (ICS) are the cornerstone of asthma maintenance treatment in children. Particularly among parents, there is concern about the safety of ICS as studies in children have shown reduced growth. Small-particle-size ICS targeting the smaller airways have improved lung deposition and effective asthma control might be achieved at lower daily doses.Ciclesonide is a relatively new ICS. This small-particle ICS is a pro-drug that is converted in the airways to an active metabolite and therefore with potentially less local (throat infection) and systemic (reduced growth) side effects. It can be inhaled once daily, thereby possibly improving adherence.. To assess the efficacy and adverse effects of ciclesonide compared to other ICS in the management of chronic asthma in children.. We searched the Cochrane Airways Group Register of trials with pre-defined terms. Additional searches of MEDLINE (via PubMed), EMBASE and Clinical study results.org were undertaken. Searches are up to date to 7 November 2012.. Randomised controlled parallel or cross-over studies were eligible for the review. We included studies comparing ciclesonide with other corticosteroids both at nominally equivalent doses or lower doses of ciclesonide.. Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials.. Six studies were included in this review (3256 children, 4 to 17 years of age). Two studies were published as conference abstracts only. Ciclesonide was compared to budesonide and fluticasone.Ciclesonide compared to budesonide (dose ratio 1:2): asthma symptoms and adverse effect were similar in both groups. Pooled results showed no significant difference in children who experience an exacerbation (risk ratio (RR) 2.20, 95% confidence interval (CI) 0.75 to 6.43). Both studies reported that 24-hour urine cortisol levels showed a statistically significant decrease in the budesonide group compared to the ciclesonide group.Ciclesonide compared to fluticasone (dose ratio 1:1): no significant differences were found for the outcome asthma symptoms. Pooled results showed no significant differences in number of patients with exacerbations (RR 1.37, 95% CI 0.58 to 3.21) and data from a study that could not be pooled in the meta-analysis reported similar numbers of patients with exacerbations in both groups. None of the studies found a difference in adverse effects. No significant difference was found for 24-hour urine cortisol levels between the groups (mean difference 0.54 nmol/mmol, 95% CI -5.92 to 7.00).Ciclesonide versus fluticasone (dose ratio 1:2) was assessed in one study and showed similar results between the two corticosteroids for asthma symptoms. The number of children with exacerbations was significantly higher in the ciclesonide group (RR 3.57, 95% CI 1.35 to 9.47). No significant differences were found in adverse effects (RR 0.98, 95% CI 0.81 to 1.14) and 24-hour urine cortisol levels (mean difference 1.15 nmol/mmol, 95% CI 0.07 to 2.23).The quality of evidence was judged 'low' for the outcomes asthma symptoms and adverse events and 'very low' for the outcome exacerbations for ciclesonide versus budesonide (dose ratio 1:1). The quality of evidence was graded 'moderate' for the outcome asthma symptoms, 'very low' for the outcome exacerbations and 'low' for the outcome adverse events for ciclesonide versus fluticasone (dose ratio 1:1). For ciclesonide versus fluticasone (dose ratio 1:2) the quality was rated 'low' for the outcome asthma symptoms and 'very low' for exacerbations and adverse events (dose ratio 1:2).. An improvement in asthma symptoms, exacerbations and side effects of ciclesonide versus budesonide and fluticasone could be neither demonstrated nor refuted and the trade-off between benefits and harms of using ciclesonide instead of budesonide or fluticasone is unclear. The resource use or costs of different ICS should therefore also be considered in final decision making. Longer-term superiority trials are needed to identify the usefulness and safety of ciclesonide compared to other ICS. Additionally these studies should be powered for patient relevant outcomes (exacerbations, asthma symptoms, quality of life and side effects). There is a need for studies comparing ciclesonide once daily with other ICS twice daily to assess the advantages of ciclesonide being a pro-drug that can be administered once daily with possibly increased adherence leading to increased control of asthma and fewer side effects.

Topics: Adolescent; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Fluticasone; Humans; Pregnenediones; Randomized Controlled Trials as Topic

Asthma is a common problem in paediatric population. International treatment guidelines recognize the role of inhaled corticosteroids for asthma in young children. Inhaled fluticasone propionate is reported to have greater systemic effects like other corticosteroids. Limited data is available on safety of this drug when used for longer duration. So, we conducted a systematic review to study the effect of inhaled fluticasone propionate on adrenal suppression, growth and bone mineral density in paediatric patients.. A systematic review.. We searched for Randomized controlled trials in MEDLINE from January 2000 to December 2012. References of included study were hand searched. Information on study design, study population, drugs and dosage used, follow up period, measures used to evaluate safety and outcomes was abstracted independently by three reviewers. DETAILS OF INCLUDED STUDIES: In all included studies, participants were asthmatic children below 18 years and treated with fluticasone propionate. Minimum follow up considered was three months and should have measured HPA suppression or growth velocity or bone mineral density.. Total ten studies were included. Studies which had monitored HPA function varied in dosage of drug, mode of administration and duration. Inspite of that it has been observed that serum cortisol level is affected by fluticasone propionate, no significant effect on bone mineral density was reported with fluticasone propionate, but the sample size was inadequate and dietary calcium intake was not recorded. None of the studies reported any significant reduction in growth when inhaled fluticasone propionate was used for the treatment of asthma, but the baseline growth and final adult height attained were not assessed.. This systematic review included only free full text articles published in English. Only randomized controlled trials were included. Cohort studies were not included.. With available evidences, the safety of inhaled fluticasone propionate cannot be questioned. This systematic review could not derive any significant adverse effect on HPA function, growth and bone mineral density in asthmatic children when used for long duration and followed for up to three months.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Body Height; Bone Density; Child; Child, Preschool; Fluticasone; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Infant; Pituitary-Adrenal System; Time Factors

The corticosteroid fluticasone propionate (fluticasone) and the long-acting β₂-adrenoceptor agonist formoterol fumarate (formoterol) have been combined in a single, pressurized, metered-dose, aerosol inhaler for the maintenance treatment of patients aged ≥12 years with persistent asthma. This article reviews the clinical efficacy and tolerability of fluticasone/formoterol, with a brief summary of pharmacodynamic and pharmacokinetic properties of the individual drugs. In well designed 8- and 12-week clinical trials in patients with asthma, twice-daily fluticasone/formoterol 100/10, 250/10 (adults and adolescents) or 500/20 μg (adults only) demonstrated rapid and sustained improvements in lung function and asthma control. Improvements achieved with the fixed combination were greater than those achieved with placebo or monotherapy with either of the same respective dosages of fluticasone or formoterol, and similar to those demonstrated when the individual components were administered via separate inhalers concurrently. The efficacy of fluticasone/formoterol was noninferior to that of fluticasone/salmeterol or budesonide/formoterol. Fluticasone/formoterol demonstrated a faster onset of bronchodilation than fluticasone/salmeterol. Fluticasone/formoterol was generally well tolerated, including during treatment periods of up to 12 months. The tolerability profile of fluticasone/formoterol was generally similar to that of fluticasone/salmeterol or budesonide/formoterol.

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Metered Dose Inhalers

Inhaled corticosteroids (ICSs) are the mainstay of anti-inflammatory treatment in subjects with asthma and COPD. This review evaluates the role of nebulizers as an alternative to inhalers for delivering ICSs in asthma and COPD. I selected 16 randomized, placebo-controlled, blinded, long-term studies, mostly carried out in asthma (n = 14) and COPD. Nebulized budesonide has been demonstrated to be effective and safe in children ages 1-8 years, and, with less evidence, in infants and adults with asthma. Other investigations, with the addition of in vitro and in vivo comparison studies, have shown that nebulized beclomethasone, fluticasone, and flunisolide are effective alternatives to nebulized budesonide in asthma and COPD. Efficient delivery of nebulized ICSs requires that the nebulizer system, the nebulized drug formulation, and the inhaling subject interact properly. The practices of mixing nebulized ICSs with bronchodilators and using nebulized ICSs in acute settings are promising, but require further confirmations, and at present cannot be recommended. I conclude that nebulizers may be considered as an effective alternative to inhalers for delivering ICSs and can be recommended to asthmatic and COPD subjects who are unwilling or unable to use inhalers. Newer formulations could possibly offer a relevant advance for a more efficient nebulization of ICSs.

Topics: Administration, Inhalation; Androstadienes; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Equipment Design; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive

The fraction of exhaled nitric oxide (FeNO) has gained interest as a non-invasive tool to measure airway inflammation in asthma since it reflects allergic inflammation. Recent controlled clinical studies have, however, questioned its role in the management of asthma in children. To assess the clinical value of FeNO in paediatric asthma management, a meta-analysis was performed on the controlled studies of childhood asthma management guided by repeated FeNO measurements, and relevant publications on the confounders of FeNO were reviewed. The data suggests that utilising FeNO to tailor the dose of inhaled corticosteroids in children cannot be recommended for routine clinical practice since there is a danger of excessive inhaled corticosteroid doses in children without meaningful changes in clinical outcomes. Many disease and non-disease related factors (most importantly atopy, height/age and infection) affect FeNO levels which can easily confound the interpretation.

Topics: Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Biomarkers; Breath Tests; Budesonide; Child; Disease Management; Fluticasone; Humans; Nitric Oxide

A recent case-controlled study reported an increased risk of diabetes mellitus in patients treated with inhaled corticosteroids for asthma or COPD, versus age-matched controls.. The purpose of the current study was to evaluate whether there was an increased risk of new onset diabetes mellitus or hyperglycaemia among patients with asthma or COPD treated with inhaled corticosteroids.. A retrospective analysis evaluated all double-blind, placebo-controlled, trials in patients ≥4 years of age involving budesonide or budesonide/formoterol in asthma (26 trials; budesonide: n = 9067; placebo: n = 5926), and in COPD (8 trials; budesonide: n = 4616; non-ICS: n = 3643). A secondary dataset evaluated all double-blind, controlled trials in asthma involving the use of inhaled corticosteroids (60 trials; budesonide: n = 33,496; fluticasone: n = 2773).. In the primary asthma dataset, the occurrence of diabetes mellitus/hyperglycaemia adverse events (AEs) was 0.13% for budesonide and 0.13% for placebo (HR 0.98 [95% CI: 0.38-2.50], p = 0.96) and serious adverse events (SAEs) was 0% for budesonide and 0.05% for placebo. In the secondary dataset, the occurrence of diabetes/hyperglycaemia as AE and SAE was 0.19% and 0.03%, respectively. In the COPD dataset, the occurrence of diabetes mellitus/hyperglycaemia AEs was 1.3% for budesonide and 1.2% for non-ICS (HR 0.99 [95% CI: 0.67-1.46], p = 0.96) and SAEs was 0.1% for budesonide and 0.03% for non-ICS.. Treatment with inhaled corticosteroids in patients with asthma or COPD was not associated with increased risk of new onset diabetes mellitus or hyperglycaemia.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Diabetes Mellitus; Double-Blind Method; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Hyperglycemia; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors

Inhaled corticosteroids (ICS) are drugs of choice for persistent asthma. Less than 500 µg/d of fluticasone are believed to be safe. We found 92 cases of adrenal suppression in PubMed; among these cases there were 13 children who took 500 µg/d or less of fluticasone. Adrenal insufficiency was diagnosed in a 7-year-old boy on 460 µg ICS for 16 months, with a diagnosis of chronic persistent asthma. A random cortisol was nondetectable as was an early morning cortisol. ICS have greatly improved the day-to-day lives of children with chronic persistent asthma. Parents of children younger than 12 years, who use at least 400 µg of inhaled fluticasone (or bioequivalent), must be given oral and written instructions about warning symptoms of hypocortisolism. Major stress such as surgery, gastrointestinal, bronchopulmonary, or other systemic infections, and heat stress may mandate a written plan of action for use by hospital physicians.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Hydrocortisone; Male; Off-Label Use

Topics: Androstadienes; Asthma; Bronchodilator Agents; Child; Fluticasone; Humans; Male; Tic Disorders; Tics

International asthma management guidelines recommend a long-acting β(2)-agonist (LABA) as add-on therapy in patients whose asthma is not controlled by low-dose inhaled corticosteroid (ICS) monotherapy. Treatment with a single inhaler containing an ICS/LABA combination is advocated because it may facilitate adherence to a regimen. When prescribing ICS/LABA combination therapy, the potency of the ICS and the speed of onset of the LABA are considered important factors; therefore, an inhaled therapy containing components with these properties may be valued by physicians. The ICS fluticasone propionate (fluticasone) has potent and sustained anti-inflammatory effects, and the LABA formoterol fumarate (formoterol) provides rapid bronchodilation; the efficacy and safety profiles of these agents have been well established in clinical practice. Fluticasone and formoterol have been combined, for the first time, in a single hydrofluoroalkane-based aerosol (flutiform®; fluticasone propionate/formoterol fumarate). Here, we review data from the published randomized, controlled, clinical trials that demonstrate the efficacy and tolerability of this product. It has been shown that fluticasone/formoterol is more efficacious than fluticasone or formoterol given alone, and provides similar improvements in lung function to fluticasone and formoterol administered concurrently via separate inhalers. Fluticasone/formoterol has similar efficacy and tolerability profiles to budesonide/formoterol and fluticasone/salmeterol, but with the additional benefit of more rapid bronchodilation than fluticasone/salmeterol.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aerosols; Androstadienes; Asthma; Bronchodilator Agents; Clinical Trials as Topic; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Randomized Controlled Trials as Topic; Treatment Outcome

Fixed-dose combinations of inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABAs) have been used to manage asthma for several years. They are the preferred therapy option for patients who do not achieve optimal control of their asthma with low-dose ICS monotherapy. In Europe, four ICS/LABA products are commercially available for asthma maintenance therapy (fluticasone propionate/formoterol fumarate, fluticasone propionate/salmeterol xinafoate, budesonide/formoterol fumarate and beclometasone dipropionate/formoterol fumarate), and other combinations are likely to be developed over the next few years (e.g. mometasone/formoterol fumarate, fluticasone furoate/vilanterol, mometasone/indacaterol). Data from randomized, controlled, clinical trials do not demonstrate a clear overall efficacy difference among ICS/LABA combinations approved for asthma therapy. Conversely, pharmacological data indicate that there may be certain advantages to using one ICS or LABA over another because of the specific pharmacodynamic and pharmacokinetic profiles associated with particular treatments. This review article summarizes the pharmacological characteristics oft he various ICSs and LABAs available for the treatment of asthma, including the potential for ICS and LABA synergy, and gives an insight into the rationale for the development of the latest ICS/LABA combination approved for asthma maintenance therapy.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Evidence-Based Medicine; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Time Factors; Treatment Outcome

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Asthma, Exercise-Induced; Child; Child, Preschool; Delayed-Action Preparations; Drug Combinations; Fluticasone; Humans; Infant; Leukotriene Antagonists; Nebulizers and Vaporizers; Salmeterol Xinafoate; Severity of Illness Index; Theophylline

Guidelines for clinical practice are expected to gather evidence-based recommendations to support optimal medical behaviours. The aim of the current review is to explore how currently available research regarding the strategy of using budesonide/formoterol (BUD/FORM) as maintenance and reliever therapy (Symbicort SMART) covers the items considered by the Grade of Recommendations, Assessment, Development and Evaluation (GRADE) system, through a comparative analysis of methodological approaches, clinical outcomes, patient-reported outcomes and costs, in order to highlight uncovered areas.. Thirteen trials providing data on 21 095 analysed patients were available. No serious limits in methodological study features were found. Evaluation of the clinical outcome was consistent with the efficacy of BUD/FORM maintenance and reliever therapy. As the time to first exacerbation was the primary outcome in most of the studies, conclusive indications cannot be drawn regarding other clinical outcomes or patient-reported outcomes, which were investigated as secondary outcomes. A comprehensive systematic review exploring all critical and important outcomes is desirable, but further research concerning the safety issues of Long Acting β2 Agonists (LABA) and patients' reported outcomes about the SMART in respect to alternative strategies is likely to affect a clear recommendation in the near future.. The efficacy of BUD/FORM maintenance and reliever therapy in extending the time to first exacerbation appears consistent between studies. Further studies exploring all patients' important outcomes are needed. Clinical and economic assessments are worthy of being investigated to verify the directness of the evidence in respect to real life patients and different geographical realities.

Topics: Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Bias; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Child; Costs and Cost Analysis; Data Collection; Disease Progression; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Europe; Evidence-Based Medicine; Fluticasone; Formoterol Fumarate; Humans; Multicenter Studies as Topic; Patient Satisfaction; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Spirometry; Time Factors; Treatment Outcome; World Health Organization

Around 5.2 million people in the UK are estimated to have asthma.1 Mortality and hospitalisation rates associated with the condition fell significantly in the last 20 years of the 20th century, but have not fallen further since then.2 In 2006, there were over 1,000 asthma deaths and around 78,000 hospital admissions due to asthma in the UK.2 One pharmacological strategy that has been developed recently to try to improve asthma management is the use of single maintenance and reliever therapy (SMART). This involves the patient using a single inhaler containing a corticosteroid (budesonide) and a long-acting beta(2) agonist (LABA; formoterol), for regular maintenance treatment, but also for additional 'rescue' use on an as-needed basis. Combination inhaler use is claimed to improve adherence, and is now included in UK asthma guidelines.3 Here we assess the evidence for single combination therapy, its relative effectiveness in comparison with other approaches, and whether or under what circumstances it should be used.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Medication Adherence; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

Long-acting beta-agonists are a common second line treatment in people with asthma inadequately controlled with inhaled corticosteroids. Single device inhalers combine a long-acting beta-agonist with an inhaled steroid delivering both drugs as a maintenance treatment regimen. This updated review compares two fixed-dose options, fluticasone/salmeterol FP/SALand budesonide/formoterol, since this comparison represents a common therapeutic choice.. To assess the relative effects of fluticasone/salmeterol and budesonide/formoterol in people with asthma.. We searched the Cochrane Airways Group register of trials with prespecified terms. We performed additional hand searching of manufacturers' web sites and online trial registries. Search results are current to June 2011.. We included randomised studies comparing fixed dose fluticasone/salmeterol and budesonide/formoterol in adults or children with a diagnosis of asthma. Treatment in the studies had to last for a minimum of 12 weeks.. Two authors independently assessed studies for inclusion in the review. We combined continuous data outcomes with a mean difference (MD), and dichotomous data outcomes with an odds ratio (OR). We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.. Five studies met the review entry criteria (5537 adults). Study populations entered the studies having previously been treated with inhaled steroids and had moderate or mild airway obstruction (mean FEV(1) predicted between 65% and 84% at baseline). Most of the studies assessed treatment over a period of six months. The studies were at a low risk of selection and performance/detection bias, although we could not determine whether missing data had an impact on the results. Availablility of outcome data was satisfactory.Primary outcomesThe odds ratio for exacerbations requiring oral steroids was lower with fluticasone/salmeterol but did not reach statistical significance (OR 0.89, 95% confidence interval (CI) 0.74 to 1.07, four studies, N = 4949). With an assumed risk with budesonide/formoterol of 106/1000 participants requiring oral steroids, treatment with fluticasone/salmeterol would lead to between 25 fewer and seven more people per 1000 experiencing a course of oral steroids. Although the odds of hospital admission was higher with fluticasone/salmeterol, this did not reach statistical significance (OR 1.29, 95% CI 0.68 to 2.47, four studies, 4879 participants). With an assumed risk in the budesonide/formoterol of 7/1000, between two fewer and 10 more people per 1000 would be hospitalised on fluticasone/salmeterol. The odds of a serious adverse event related to asthma was higher with fluticasone/salmeterol but did not differ significantly between treatments (OR 1.47, 95% CI 0.75 to 2.86, three studies, 4054 participants). With an assumed risk in the budesonide/formoterol of 7/1000, between two fewer and 13 more people per 1000 would experience a serious adverse event on fluticasone/salmeterol.Secondary outcomesLung function outcomes, symptoms, rescue medication, composite of exacerbations leading to either emergency department visit or hospital admission, withdrawals and adverse events did not differ statistically between treatments. Assessment of quality of life was limited to two studies, both of which gave results that did not reach statistical significance. One study reported one death out of 1000 participants on fluticasone/salmeterol and no deaths in a similar number of participants treated with budesonide/formoterol. No deaths were reported in the other studies.. Statistical imprecision in the effect estimates for exacerbations and serious adverse events do not enable us to conclude that either therapy is superior. The uncertainty around the effect estimates justify further trials to provide more definitive conclusions; the overall quality of evidence based on GRADE recommendations for the three primary outcomes and withdrawals due to serious adverse events was moderate. We rated the quality of evidence for mortality to be low. Results for lung function outcomes showed that the drugs were sufficiently similar that further research is unlikely to change the effects. No trials were identified in the under-12s and research in this population is a high priority. Evaluation of quality of life is a priority for future research.

Topics: Adolescent; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

There is concern that long-acting beta agonist (LABA) drugs may increase the risk of asthma mortality.. A meta-analysis was conducted of asthma deaths in randomised controlled clinical trials from the GlaxoSmithKline database that compared salmeterol with a non-LABA comparator treatment in asthma. The Peto one-step method was used to determine the risk overall (all studies) and in derived datasets based on inhaled corticosteroid (ICS) use.. There were 35 asthma deaths in 215 studies with 106,575 subjects. Two studies (SMART and SNS) contributed 30/35 (86%) asthma deaths, the overall findings largely reflecting the characteristics of these studies. The odds ratio for risk of asthma mortality with salmeterol was 2.7 (95% CI 1.4 to 5.3). In 54 placebo controlled studies the risk of death from asthma in patients not prescribed ICS was 7.3 (95% CI 1.8 to 29.4). In 127 studies in which patients were prescribed ICS, the risk of asthma death was 2.1 (95% CI 0.6 to 7.9). In 63 studies in which patients were randomised to receive the combination salmeterol/fluticasone propionate inhaler or ICS, there were no asthma deaths among 22,600 patients.. Salmeterol monotherapy in asthma increases the risk of asthma mortality and this risk is reduced with concomitant ICS therapy. There is no evidence that combination salmeterol/fluticasone propionate therapy is associated with an increased risk of asthma mortality, although this interpretation is limited by the low statistical power of available studies.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Epidemiologic Methods; Fluticasone; Humans; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

An increase in serious adverse events with both regular formoterol and regular salmeterol in chronic asthma has been demonstrated in comparison with placebo in previous Cochrane reviews. This increase was significant in trials that did not randomise participants to an inhaled corticosteroid, but less certain in the smaller numbers of participants in trials that included an inhaled corticosteroid in the randomised treatment regimen.. We set out to compare the risks of mortality and non-fatal serious adverse events in trials which have randomised patients with chronic asthma to regular formoterol versus regular salmeterol, when each are used with an inhaled corticosteroid as part of the randomised treatment.. Trials were identified using the Cochrane Airways Group Specialised Register of trials. Manufacturers' web sites of clinical trial registers were checked for unpublished trial data and Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol were also checked. The date of the most recent search was July 2009.. Controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma were included if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid), and were of at least 12 weeks duration.. Two authors independently selected trials for inclusion in the review and extracted outcome data. Unpublished data on mortality and serious adverse events were sought from the sponsors and authors.. Eight studies met the eligibility criteria of the review recruiting 6,163 adults and adolescents. There were seven studies (involving 5,935 adults and adolescents) comparing formoterol and budesonide to salmeterol and fluticasone. All but one study administered the products as a combined inhaler, and most used formoterol 50 mcg and budesonide 400 mcg twice daily versus salmeterol 50 mcg and fluticasone 250 mcg twice daily. There were two deaths overall (one on each combination) and neither were thought to be related to asthma.There was no significant difference between treatment groups for non-fatal serious adverse events, either all-cause (Peto OR 1.14; 95% CI 0.82 to 1.59, I(2) = 26%) or asthma-related (Peto OR 0.69; 95% CI 0.37 to 1.26, I(2) = 33%). Over 23 weeks the rates for all-cause serious adverse events were 2.6% on formoterol and budesonide and 2.3% on salmeterol and fluticasone, and for asthma-related serious adverse events, 0.6% and 0.8% respectively.There was one study (228 adults) comparing formoterol and beclomethasone to salmeterol and fluticasone, but there were no deaths or hospital admissions.No studies were found in children.. The seven identified studies in adults did not show any significant difference in safety between formoterol and budesonide in comparison with salmeterol and fluticasone. Asthma-related serious adverse events were rare, and there were no reported asthma-related deaths. There was a single small study comparing formoterol and beclomethasone to salmeterol and fluticasone in adults, but no serious adverse events occurred in this study. No studies were found in children.Overall there is insufficient evidence to decide whether regular formoterol and budesonide or beclomethasone have equivalent or different safety profiles from salmeterol and fluticasone.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

The objective of this study was to analyse inter-and intra-country quantitative and qualitative differences in anti-asthmatic prescriptions to children and adolescents.. A literature search was performed in EMBASE and MEDLINE to identify pharmaco-epidemiological studies published from January 1, 2000 to December 31, 2008 in which anti-asthmatic prescription prevalence in out-hospital children was measured. A meta-analytic weighted average and 95% confidence intervals of prescription prevalences were calculated using a random-effect(s) model. Inter- and intra-country quantitative and, where possible, qualitative prescribing patterns were compared and assessed.. Twelve studies were identified (ten from Europe, one from Canada and one from the USA), but epidemiological indicators varied widely, and only eight were suitable for meta-analysis. The data from these studies revealed inter-country quantitative differences in prescription prevalences in the overall population

Topics: Acetates; Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Canada; Child; Cromolyn Sodium; Cyclopropanes; Drug Prescriptions; Ethanolamines; Europe; Fluocinolone Acetonide; Fluticasone; Humans; Italy; Prevalence; Quinolines; Salmeterol Xinafoate; Sulfides; United States

To compare the efficacy of inhaled corticosteroids in infants and preschoolers with recurrent wheezing or asthma.. Randomized, prospective, controlled trials published January 1996 to March 2008 with a minimum of 4 weeks of inhaled corticosteroids versus placebo were retrieved through Medline, Embase, and Central databases. The primary outcome was wheezing/asthma exacerbations; secondary outcomes were withdrawal caused by wheezing/asthma exacerbations, changes in symptoms score, pulmonary function (peak expiratory flow and forced expiratory volume in 1 second), or albuterol use.. Of eighty-nine studies identified, 29 (N = 3592 subjects) met the criteria for inclusion. Patients who received inhaled corticosteroids had significantly less wheezing/asthma exacerbations than those on placebo (18.0% vs 32.1%); posthoc subgroup analysis suggests that this effect was higher in those with a diagnosis of asthma than wheeze but was independent of age (infants versus preschoolers), atopic condition, type of inhaled corticosteroid (budesonide metered-dose inhaler versus fluticasone metered-dose inhaler), mode of delivery (metered-dose inhaler versus nebulizer), and study quality (Jadad score: <4 vs >/=4) and duration (<12 vs >/=12 weeks). In addition, children treated with inhaled corticosteroids had significantly fewer withdrawals caused by wheezing/asthma exacerbations, less albuterol use, and more clinical and functional improvement than those on placebo.. Infants and preschoolers with recurrent wheezing or asthma had less wheezing/asthma exacerbations and improve their symptoms and lung function during treatment with inhaled corticosteroids.

Topics: Adrenal Cortex Hormones; Androstadienes; Asthma; Beclomethasone; Budesonide; Child, Preschool; Fluticasone; Humans; Infant; Lung Volume Measurements; Metered Dose Inhalers; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Respiratory Sounds; Secondary Prevention

For many years, chronic obstructive pulmonary disease (COPD) was considered a disease of fixed airflow obstruction for which there was no good treatment. Out of desperation and frustration, health care providers extrapolated from asthma to COPD, and standard asthma therapy was adopted without evidence for efficacy. In recent years, we have gained a better understanding of the pathophysiologic differences between asthma and COPD, and prospective controlled trials have provided a rationale for therapy. Smoking cessation is critically important, both as primary prevention and as an effective way to slow the decrease in lung function in patients with established disease. beta(2)-Adrenergic and anticholinergic agonists improve lung function and relieve symptoms in most patients. Tiotropium improves exercise tolerance and quality of life and reduces exacerbations and hospitalizations. The increase in lung function seen with tiotropium is sustained with continued use over at least 3 to 4 years. Inhaled corticosteroids decrease exacerbations and improve quality of life, and their effect seems greatest in patients with lower lung function and in exacerbation-prone patients. There is no evidence that inhaled corticosteroids alone affect mortality, despite the reduction in exacerbations and increased risk of pneumonia. In some patient populations, inhaled fluticasone, salmeterol, or the combination might slow the rate of loss of lung function. Rather than reflexively using effective asthma therapy in the patient with COPD, current and future therapy for COPD is increasingly evidence based and targeted to specific inflammatory pathways that are important in patients with COPD.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Antagonists; Albuterol; Androstadienes; Antioxidants; Asthma; Bacterial Vaccines; Bronchodilator Agents; Clinical Trials as Topic; Fluticasone; Humans; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide; Viral Vaccines

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Drug Combinations; Ethanolamines; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Middle Aged; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Treatment Outcome

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Fluticasone; Glucocorticoids; Humans; Japan; Pediatrics; Practice Guidelines as Topic; Severity of Illness Index

Topics: Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Chronic Disease; Clenbuterol; Cough; Drug Therapy, Combination; Fluticasone; Histamine H1 Antagonists; Humans; Hypersensitivity, Immediate; Phthalazines; Prednisolone

Combination therapies are frequently recommended as maintenance therapy for people with asthma, whose disease is not adequately controlled with inhaled steroids. Fluticasone/salmeterol (FP/SAL) and budesonide/formoterol (BUD/F) have been assessed against their respective monocomponents, but there is a need to compare these two therapies on a head-to-head basis.. To estimate the relative effects of fluticasone/salmeterol and budesonide/formoterol in terms of asthma control, safety and lung function.. We searched the Cochrane Airways Group register of trials with prespecified terms. We performed additional hand searching of manufacturers' web sites and online trial registries. Searches are current to May 2008.. Randomised studies comparing fixed dose FP/SAL and BUD/F were eligible, for a minimum of 12 weeks. Crossover studies were excluded. Our primary outcomes were: i) exacerbations requiring oral steroid bursts, ii) hospital admission and iii) serious adverse events.. Two authors independently assessed studies for inclusion in the review. We combined continuous data outcomes with a mean difference (MD), and dichotomous data outcomes with an odds ratio (OR).. Five studies met the review entry criteria (5537 participants).. The odds of an exacerbation requiring oral steroids did not differ significantly between treatments (OR 0.89; 95% CI 0.73 to 1.09, three studies, 4515 participants). The odds of an exacerbation leading hospital admission were also not significantly different (OR 1.29; 95% CI 0.68 to 2.47, four studies, 4879 participants). The odds of serious adverse events did not differ significantly between treatments (OR 1.47; 95% CI 0.75, 2.86, three studies, 4054 participants).. Lung function outcomes, symptoms, rescue medication, exacerbations leading ED visit/hospital admission and adverse events were not significantly different between treatments.. The evidence in this review indicates that differences in the requirement for oral steroids and hospital admission between BUD/F and FP/SAL do not reach statistical significance. However, the confidence intervals do not exclude clinically important differences between treatments in reducing exacerbations or causing adverse events. The width of the confidence intervals for the primary outcomes justify further trials in order to better determine the relative effects of these drug combinations. Although this review sought to assess the effects of these drugs in both adults and children, no trials were identified in the under-12s and research in this area is of a high priority.

Topics: Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment of asthma.. To assess efficacy and safety outcomes in studies that compared FP to placebo for treatment of chronic asthma.. We searched the Cochrane Airways Group Specialised Register (January 2008), reference lists of articles, contacted trialists and searched abstracts of major respiratory society meetings (1997-2006).. Randomised trials in children and adults comparing FP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and risk of bias.. Two review authors extracted data. Quantitative analyses were undertaken using Review Manager software.. Eighty-six studies met the inclusion criteria, recruiting 16,160 participants. In non-oral steroid treated asthmatics with mild and moderate disease FP resulted in improvements from baseline compared with placebo across all dose ranges (100 to 1000 mcg/d) in FEV1 (between 0.1 to 0.43 litres); morning PEF (between 23 and 46 L/min); symptom scores (based on a standardised scale, between 0.44 and 0.7); reduction in rescue beta-2 agonist use (between 1 and 1.4 puffs/day). High dose FP increased the number of patients who could withdraw from prednisolone: FP 1000-1500 mcg/day Peto Odds Ratio 14.07 (95% CI 7.17 to 27.57). FP at all doses led to a greater likelihood of sore throat, hoarseness and oral Candidiasis.. Doses of FP in the range 100-1000 mcg/day are effective. In most patients with mild-moderate asthma improvements with low dose FP are only a little less than those associated with high doses when compared with placebo. High dose FP appears to have worthwhile oral-corticosteroid reducing properties. FP use is accompanied by an increased likelihood of oropharyngeal side effects.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Chronic Disease; Fluticasone; Humans; Placebos; Randomized Controlled Trials as Topic

Inhaled fluticasone propionate (FP) is a high-potency inhaled corticosteroid used in the treatment of asthma.. 1. To assess the efficacy and safety outcomes of inhaled fluticasone at different nominal daily doses in the treatment of chronic asthma.2. To test for the presence of a dose-response effect.. We searched the Cochrane Airways Group Trials Register (January 2008).. Randomised trials in children and adults comparing fluticasone at different nominal daily doses in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One review author extracted data. These were checked and verified by a second reviewer. Quantitative analyses where undertaken using Review Manager.. Fifty-one published and unpublished trials (representing 55 group comparisons, 10,797 participants) met the inclusion criteria. In asthmatics with mild to moderate disease who were not on oral steroids, FP did not exhibit a dose-response effect in the lower dose comparisons in FEV1 (50mcg, 100mcg, 200mcg and 4-500mcg daily). There were no statisitically significant differences between 4-500mcg and 800-1000mcg, and between 50-100 and 800-1000mcg of FP. When 200mcg was compared with 800-1000mcg daily FEV1 favoured the four/five fold increase. For PEF, a dose response was present with FP when low and moderate, and low and high doses of FP were compared. There was no evidence of a dose-response effect on symptoms or rescue beta-2 agonist use. The likelihood of hoarseness and oral candidiasis was significantly greater for the higher doses (800 to 1000 microg/day). People with oral steroid-dependent asthma treated with FP (2000 microg/day) were significantly more likely to reduce oral prednisolone than those on 1000 to 1500 microg/day (Peto odds Ratio 2.8, 95% CI 1.3 to 6.3). The highest dose also allowed a significant reduction in daily oral prednisolone dose compared to 1000 to 1500 microg/day (WMD 2.0 mg/day, 95% CI 0.1 to 4.0 mg/day).. We have not found evidence of a pronounced dose response in FEV1 with increasing doses of fluticasone. The number of studies contributing to our primary outcomes was low. At dose ratios of 1:2, there are statistically significant differences in favour of the higher dose in morning peak flow across the low dose range. The clinical impact of these differences is open to interpretation. Patients with moderate disease achieve similar levels of asthma control on medium doses of fluticasone (400 to 500 microg/day) as they do on high doses (800 to 1000 microg/day). More work in severe asthma would help to confirm that doses of FP above 500 microg/day confer greater benefit in this subgroup than doses of around 200 microg/day. In oral corticosteroid-dependent asthmatics, reductions in prednisolone requirement may be gained with FP 2000 microg/day.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Chronic Disease; Fluticasone; Humans; Randomized Controlled Trials as Topic

Orally inhaled corticosteroids represent the usually recommended initial controller therapy for most patients with persistent asthma. Some patients might benefit from earlier use of a combination of an inhaled corticosteroid and an orally inhaled long-acting beta agonist, however. We wished to identify clinical characteristics of patients which would enable one to identify a sub-group of patients who would benefit most from initiating sustained controller therapy with combination therapy.. We carried out a secondary analysis of five randomized clinical trials including 1606 subjects in order to examine whether differences in baseline characteristics of patients might predict a greater preferential response to combination therapy with salmeterol and fluticasone.. Subjects whose asthma had been present for 10 or more years were 2.2 times more likely to achieve well-controlled asthma by 12 weeks on combination therapy, while subjects with a shorter duration of asthma were only 1.4 times as likely to achieve asthma control with combination therapy as opposed to inhaled corticosteroids alone. None of the other factors examined including symptom frequency or severity, rescue beta-agonist use, severity of lung function impairment or degree of reversibility, was able to distinguish subjects who would benefit preferentially from such combination therapy.. Longer duration of asthma might be used to identify subjects who will benefit more from combined maintenance therapy with a long-acting beta agonist and an inhaled corticosteroid rather than an inhaled corticosteroid alone.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Treatment Outcome

According to current guidelines, inhaled corticosteroids (ICS) are the preferred primary long-term treatment for asthmatic children of all age groups, but leukotriene receptor antagonists can be considered to be an alternative treatment for mild persistent asthma. In this article, all randomized double-blind efficacy studies comparing the long-term (>4-week) treatment using a leukotriene receptor antagonist with an inhaled corticosteroid in asthmatic children were critically reviewed. In school-aged children, five reports with an adequate study design were available. All of these studies compared montelukast with inhaled fluticasone. The meta-analysis of the two main outcome measures, forced expiratory volume in 1 s (weighted mean difference, 4.6% predicted, 95% confidence interval: 3.5-5.5) and asthma control days (respectively, 5.6%, 4.3-6.9) demonstrated the superiority of fluticasone over montelukast. Many other clinical and pulmonary outcomes also consistently showed that low-dose inhaled fluticasone was more effective than montelukast in the long-term management of mild to moderate persistent asthma. A more favorable response to fluticasone over montelukast was associated with more severe disease or markers of allergic inflammation. About a quarter of patients benefited more from montelukast than fluticasone. In children under school age, no comparative studies were available. However, long-term montelukast treatment was found to be effective in placebo-controlled studies in asthmatic children aged >2 years. These findings support the present international recommendations for ICS as the preferred first-line controller therapy for mild to moderate persistent childhood asthma. If montelukast is selected as a monotherapy and asthma is not adequately controlled within 4-6 weeks, the treatment should be discontinued and the preferred medication initiated.

Topics: Acetates; Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Androstadienes; Asthma; Bronchodilator Agents; Child; Child, Preschool; Cyclopropanes; Fluticasone; Humans; Infant; Leukotriene Antagonists; Quinolines; Randomized Controlled Trials as Topic; Sulfides; Treatment Outcome

Inhaled corticosteroids (ICS) are an integral part of asthma management, and act as an anti-inflammatory agent in the airways of the lung. These agents confer both significant benefit in terms of symptom management and improvement in lung function, but may also cause harm in terms of local and systemic side-effects. Ciclesonide is a novel steroid that is metabolised to its active component in the lung, making it a potentially useful for reducing local side effects.. To assess the efficacy and adverse effects of ciclesonide relative to those of other inhaled corticosteroids in the management of chronic asthma.. We searched the Cochrane Airways Group register of trials with pre-defined terms. Additional searches of PubMed and Clinicalstudyresults.org were undertaken. The literature searches for this review are current up to June 2007.. Randomised parallel or crossover studies were eligible for the review. We included studies comparing ciclesonide with other steroids both at nominally equivalent dose or lower doses of ciclesonide.. Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials.. Twenty one trials involving 7243 participants were included. Equal daily doses of ciclesonide and beclomethasone (BDP) or budesonide (BUD) gave similar results for peak expiratory flow rates (PEF), although forced vital capacity (FVC) was higher with ciclesonide. Data on forced expired volume in one second (FEV1) were inconsistent. Withdrawal data and symptoms were similar between treatments. Compared with the same dose of fluticasone (FP), data on lung function parameters (FEV1, FVC and PEF) did not differ significantly. Paediatric quality of life score favoured ciclesonide. Candidiasis was less frequent with ciclesonide, although other side-effect outcomes did not give significant differences in favour of either treatment. When lower doses of ciclesonide were compared to BDP or BUD, the difference in FEV1 did not reach significance but we cannot exclude a significant effect in favour of BDP/BUD. Other lung function outcomes did not give significant differences between treatments. Paediatric quality of life scores did not differ between treatments. Adverse events occurred with similar frequency between ciclesonide and BDP/BUD. Comparison with FP at half the nominal dose was undertaken in three studies, which indicated that FEV1 was not significantly different, but was not equivalent between the treatments (per protocol: -0.05 L 95% confidence intervals -0.11 to 0.01).. The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Pregnenediones; Randomized Controlled Trials as Topic

An inhaled corticosteroid (ICS) or an ICS/long-acting beta(2)-agonist (LABA) combination plus short-acting beta(2)-agonist (SABA) as needed for symptom relief is recommended for persistent asthma. Additionally, budesonide/formoterol maintenance and reliever therapy (Symbicort) SMART, AstraZeneca, Sweden) has been approved for adults in the European Union. This option is well tolerated and offers greater reductions in asthma exacerbations together with similar improvements in daily symptom control, at a lower overall steroid load, compared with fixed-dose ICS/LABA plus SABA.. Two large clinical trials investigated the use of budesonide/formoterol as maintenance and reliever compared with medium or high doses of an ICS/LABA combination as controller plus SABA as reliever in adults (aged >or= 18 years). COMPASS was a 6-month, double-blind, randomized trial, while COSMOS was a 1-year, dose titration study which reflected routine clinical practice.. Among adults, the studies confirmed a 21-39% reduction in severe exacerbations in patients treated with budesonide/formoterol maintenance and reliever therapy compared with titrated salmeterol/fluticasone plus SABA (COSMOS) or fixed higher budesonide/formoterol or salmeterol/fluticasone plus SABA (COMPASS), respectively. Similar levels of daily asthma control were achieved with budesonide/formoterol maintenance and reliever therapy at a significantly lower overall steroid load compared with salmeterol/fluticasone or budesonide/formoterol plus SABA. Budesonide/formoterol maintenance and reliever therapy was as well tolerated as combination therapies.. In adult patients, budesonide/formoterol maintenance and reliever therapy is a safe and simplified approach to asthma management, using a single inhaler, which reduces severe exacerbations and maintains similar daily asthma control at a lower drug load compared with the traditional strategy of ICS/LABA plus SABA.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Clinical Trials as Topic; Drug Combinations; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Salmeterol Xinafoate; Treatment Outcome

Although results from a few meta-analyses were most uniformly supportive of the beneficial effect of combination therapy on lung function, there were inconsistent results on other endpoints such as asthma exacerbation. Single inhalers of salmeterol and fluticasone propionate have been available, and some studies compared the effect of combination products with increased doses of inhaled corticosteroids (ICSs) on several outcome variables.. We reviewed the studies systematically, providing a quantitative summary estimate on the efficacy and safety measures of the combination products.. We searched databases (Medline and Embase) from January 1997 to December 2005 using 'fluticasone and salmerterol' or 'Seretide' or 'Advair', in combination with 'randomized controlled trial'. The databases of GlaxoSmithKline Clinical Trial Register and Cochrane Controlled Trials Register, or relevant articles were searched for additional studies.. Combination products had a comparatively low, but significant improvement in pulmonary function, with morning peak expiratory flow (PEF), evening PEF and FEV1 increasing by 17.86 liters/min, 15.57 liters/min and 0.09 liter, respectively, compared with increased doses of inhaled corticosteroid (ICSs) over 12 weeks' treatment. But there were no statistically significant differences in other endpoints such as asthma exacerbation, overall withdrawal and drug-related adverse events, with the exception of overall adverse events and symptom free 24 h, which favored combination products.. Thecombination products provided a statistically significant improvement in lung function and in symptoms but provided no significantly increased protection against exacerbation. Unless high doses of ICSs are required, there is insufficient evidence at present to recommend the use of combination products rather than increased moderate doses of ICSs as a first-line treatment for patients uncontrolled on their current doses of ICSs.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Controlled Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fluticasone; Glucocorticoids; Humans; Salmeterol Xinafoate; Treatment Outcome

The known efficacy of fluticasone propionate in adults, comparable at half-dosage of corticosteroids has been validated by the market authorization (MA) and by the national and international guidelines for beclomethasone. This could be partly explained by its pharmacological properties, affinity for glucocorticosteroid receptors, lung deposition and lipophilicity. The limited systemic adverse events is due to its low bioavailability, optimal hepatic clearance, high plasma protein binding. The efficacy in asthmatic children has been confirmed in clinical studies showing a "plateau" efficacy between 100 and 200 microg/d for the majority of children. Most children are controlled by such dosages: the added value of increasing posology on asthma control exists but is small. A high off-label posology does not allow more quickly asthma control and therefore is not justified. A twice daily dosing is more efficient, particularly for initiation of maintenance therapy, than a once daily dosing. A literature survey confirms that, at MA recommended daily doses in children (100-200 microg), fluticasone propionate has no clinically significant effect either on hypothalamic-pituitary-adrenal (HPA) axis (basal function or stimulation tests), bone or growth velocity. However, high daily doses (higher to 500 microg/day) for long periods expose to systemic adverse effects with measurable consequences on growth rate, bone density (decreasing biochemical makers of bone formation) and HPA function. Several cases of adrenal insufficiency that may have led to acute adrenal crisis have been reported in 4- to 10-year-old children receiving fluticasone propionate in doses between 500 to 2000 microg daily. In case of surgery or infection, a preventive treatment of adrenal insufficiency with hydrocortisone should be proposed for children treated for more than 6 months with such high daily doses. Such children need definitely an advice from paediatricians specialized in chest diseases as well as in endocrinology. It is important to recall that the clinical benefit of daily doses of inhaled corticosteroids higher than recommended is low and that the good use of inhaled corticosteroids particularly in children lays on the careful search of the minimal efficient daily doses.

Topics: Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biological Availability; Bronchodilator Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Fluticasone; Humans; Infant; Practice Guidelines as Topic

Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma. Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays.. To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma.. We searched the Cochrane Airways Group trial register (January 2007) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2006).. Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma.. Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data. Quantitative analyses were undertaken using RevMan analyses 1.0.1.. Seventy-one studies (14,602 participants) representing 74 randomised comparisons met the inclusion criteria. Methodological quality was fair. Dose ratio 1:2: FP produced a significantly greater end of treatment FEV1 (0.04 litres (95% CI 0 to 0.07 litres), end of treatment and change in morning PEF, but not change in FEV1 or evening PEF. This applied to all drug doses, age groups, and delivery devices. No difference between FP and BDP/BUD were seen for trial withdrawals. FP led to fewer symptoms and less rescue medication use. When given at half the dose of BDP/BUD, FP led to a greater likelihood of pharyngitis. There was no difference in the likelihood of oral candidiasis. Plasma cortisol and 24 hour urinary cortisol was measured frequently but data presentation was limited. Dose ratio 1:1: FP produced a statistically significant difference in morning PEF, evening PEF, and FEV1 over BDP or BUD. The effects on exacerbations were mixed. There were no significant differences incidence of hoarseness, pharyngitis, candidiasis, or cough.. Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing sore throat and when given at the same daily dose leads to increased hoarseness. There are concerns about adrenal suppression with Fluticasone given to children at doses greater than 400 mcg/day, but the randomised trials included in this review did not provide sufficient data to address this issue.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Randomized Controlled Trials as Topic

Patients with asthma and COPD commonly use inhaled drugs. The 3 types of currently available devices for inhaled therapy (Metered-dose inhaler, dry powder inhaler, and nebulizer) are clinically equivalent. However, since many different inhalers are available for inhaled therapy, the choice of the delivery device is important for optimizing the results of aerosol therapy. Traditional press-and-breathe Metered Dose Inhalers (pMDIs) have recently improved their ecological appeal, can be used in every clinical and environmental situation, their dosing is convenient and highly reproducible, but their efficient delivery remains highly technique dependent. Poor inhalation technique can be minimised by the use of add-on valved holding chambers, which are seldom used in the clinical practice possibly because they are cumbersome. Breath Actuated devices (BAIs), such as Dry Powder Inhalers (DPIs), which are environmental-friendly, safe, effective, reliable, portable and self-contained, overcome problems of handbreath co-ordination associated with pMDIs usage, but their use is also undermined by common errors of inhalation technique in real life. Nebulizers are cumbersome and time-comsuming for use and maintenance, but their use needs less cooperation than inhalers. Although nebulizer practice is not always evidence-based, some patients, mainly elderly prefer nebulizers for regular long-term usage. Despite the introduction of newer devices, clear advantages of a particular delivery system over other inhalers in terms of compliance, preference, and cost-effectiveness are not currently available. The objective of an ideal and easy-to use inhaler is far from reality. Patient education is the critical factor in the use and misuse of delivery devices and effectiveness of aerosol therapy. The choice of the device has to be tailored according to the patient's needs, situation, and preference. Whatever the chosen inhaler, education from health caregivers has a key-role for improving inhaler technique and compliance. Differences among delivery devices represent another challenge to patient use and caregiver instruction.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aerosols; Aged; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Caregivers; Child; Fluticasone; Follow-Up Studies; Humans; Metered Dose Inhalers; Nebulizers and Vaporizers; Patient Compliance; Patient Education as Topic; Patient Satisfaction; Physicians; Practice Guidelines as Topic; Pulmonary Disease, Chronic Obstructive; Respiratory Therapy; Salmeterol Xinafoate; Time Factors

The relative efficacy of fluticasone (FP) and beclomethasone (BDP) propelled with CFCs has been well established. The potency of HFA-BDP is thought to have been improved with new propellant and some studies suggest that it may equipotent at half the dose of CFC propelled-BDP. There is a need to revisit this question in the light of a potentially more potent new non-CFC propellant.. To determine the relative efficacy of FP and HFA-propelled BDP in chronic asthma.. The Cochrane Airways Group Specialised Register was searched using pre-specified terms. Searches were current as of January 2006.. Randomised controlled trials were eligible for inclusion in the review. We compared either CFC or HFA-propelled FP with HFA-propelled BDP. We made a distinction between HFA-BDP and HFA-BDP extra fine, which dispenses smaller particles of drug, leading to different, usually more peripheral distribution in the airways. Any inhaler device was considered, and there was no restriction on studies with or without spacers. We included studies which assessed HFA-BDP given via either pMDI, breath-actuated MDI, or DPI.. Two reviewers independently assessed studies for inclusion in the review. Data were extracted and entered in to RevMan 4.2 using standard meta-analytical techniques with predefined criteria for exploring statistical heterogeneity.. Eight studies (1260 participants) met the inclusion criteria of the review. One study was conducted in children. Study reporting quality was fair, but all studies were of short duration (three to twelve weeks). Only studies assessing HFA-BDP extra fine in comparison with FP were identified. Lung function was not significantly different between extra fine BDP and FP when compared at the same dose in parallel studies, change in FEV1: 0.04 litres (95% CI -0.03 to 0.11 litres; three studies, 659 adults); change in am PEF: -0.69 litres (95% CI -11.21 to 9.83 litres; two studies, 364 adults). Individual studies reported non-significant findings in symptom scores and quality of life questionnaires. There was no significant difference between FP and HFA-BDP in the risk of study withdrawal, dysphonia or when data were reported as any adverse event.. There was no significant difference between FP and extra fine HFA-BDP on FEV(1) or peak flow at a dose ratio of 1:1. However, the number of studies and width of the confidence intervals in the analyses do not exclude a clinically meaningful difference between these two drugs. Difficulty in the successful manipulation of the devices studied may be a barrier to the widespread use of MDIs. One paediatric study was included in the review, so extrapolation of the findings of this review to children is limited. Further longer term studies in adults and children with moderate and severe asthma are required.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; Chronic Disease; Fluticasone; Humans; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic

The dose-response relationship of inhaled fluticasone propionate (FP) for adrenal suppression in adults with asthma is not clear. The current authors carried out a systematic review and meta-analysis of placebo-controlled randomised dose-response studies of >or=4 weeks' duration, which assessed the adrenal effects of FP by cosyntropin stimulation tests in adult asthma. The main outcome measure was the proportion of subjects with adrenal function below the lower limit of the normal range. Five studies, with a total of 732 subjects with asthma, met the inclusion criteria. Data on daily doses >1,000 mug were limited to one study. The proportion of subjects with adrenal function below the lower limit of the normal range on placebo was 3.9%; for a 500-microg per day increase in FP dose the odds of an abnormality increased by 1.38 (95% confidence interval 1.01-1.59). The continuous secondary outcome measures showed an inverse linear relationship with the FP dose up to 2,000 microg.day(-1). In conclusion, for routine prescribing within the established therapeutic dose-response range (50-500 microg.day(-1)), fluticasone propionate has minimal effects on adrenal function. This conclusion is limited by the paucity of long-term studies of daily doses of fluticasone propionate >1,000 mug and by the considerable individual variability in the response.

Topics: Adrenal Insufficiency; Adult; Androstadienes; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Fluticasone; Humans; Randomized Controlled Trials as Topic

Inhaled corticosteroids (ICSs) are the most potent anti-inflammatory choice for patients with asthma. Selecting the most appropriate ICS for a patient requires a thorough understanding of the pharmacologic properties of each drug.. This review details the pharmacologic properties of ciclesonide (CIC) and fluticasone propionate (FP) and reviews the available data on suppression of the hypothalamic-pituitary-adrenal axis as a measure of systemic exposure and safety profile.. Clinical studies and case reports were identified through a MEDLINE and EMBASE search of English-language articles. The databases were searched for the years 1990 to April 2005 using the terms ciclesonide, fluticasone, ICS, and adrenal suppression. All studies were clinical trials of pharmacologic properties of the ICSs in humans.. A total of 1082 articles were identified. CIC and FP are 2 of the most potent ICSs. Both have high receptor-binding affinities (12 times and 18 times that of dexamethasone, respectively), and both may provide enhanced respiratory effects through a prolonged pulmonary residence time. The CIC metered dose inhaler dispenses smaller and more highly respirable particles than FP (1.1-2.1 pm vs 2.8-3.2 microm, respectively). Therefore, a greater percentage of administered CIC is topically deposited in the lungs (52% vs 12% to 13% for FP). CIC is delivered as an inactive parent compound, which is converted to its active metabolite, desisobutyryl-CIC (des-CIC), by esterases in the airways. More than 50% of a dose of CIC is deposited and distributed evenly throughout the lungs of healthy adults; lipid conjugation in the lung also may increase lung residence time. On entering the systemic circulation, both corticosteroids are rapidly cleared by the liver (elimination half-life of 3.5 hours for CIC vs 7.8 hours for FP). However, plasma protein binding is greater with CIC/des-CIC (99%/ approximately 99%) than FP (90%), resulting in reduced amounts of des-CIC (660 pg/d) may result in adrenal suppression. CIC has not been reported to produce any significant adrenal suppression throughout its studied dose range (up to 1280 micro/d).. A review of the literature suggests that CIC, as compared with FP, achieves greater pulmonary deposition, causes fewer adverse oropharyngeal effects, deposits less biologically active drug in the systemic circulation, and has less potential for adrenal suppression.

Topics: Adrenal Cortex Hormones; Androstadienes; Asthma; Fluticasone; Half-Life; Humans; Hypothalamo-Hypophyseal System; Metered Dose Inhalers; Pituitary-Adrenal System; Pregnenediones

Ciclesonide is a new inhaled corticosteroids licensed for the prophylactic treatment of persistent asthma in adults. Currently beclomethasone dipropionate, budesonide and fluticasone propionate are the most commonly prescribed inhaled corticosteroids for the treatment of asthma but there has been no systematic review comparing the effectiveness and safety ciclesonide to these agents. We therefore aimed to systematically review published randomised controlled trials of the effectiveness and safety of ciclesonide compared to alternative inhaled corticosteroids in people with asthma.. We performed literature searches on MEDLINE, EMBASE, PUBMED, the COCHRANE LIBRARY and various Internet evidence sources for randomised controlled trials or systematic reviews comparing ciclesonide to beclomethasone or budesonide or fluticasone in adult humans with persistent asthma. Data was extracted by one reviewer.. Five studies met the inclusion criteria. Methodological quality was variable. There were no trials comparing ciclesonide to beclomethasone. There was no significant difference between ciclesonide and budesonide or fluticasone on the following outcomes: lung function, symptoms, quality of life, airway responsiveness to a provoking agent or inflammatory markers. However, the trials were very small in size, increasing the possibility of a type II error. One trial demonstrated that the combined deposition of ciclesonide (and its active metabolite) in the oropharynx was 47% of that of budesonide while another trial demonstrated that the combined deposition of ciclesonide (and its active metabolite) in the oropharynx was 53% of that of fluticasone. One trial demonstrated less suppression of cortisol in overnight urine collection after ciclesonide compared to fluticasone (geometric mean fold difference = 1.5, P < 0.05) but no significant difference in plasma cortisol response.. There is very little evidence comparing CIC to other ICS, restricted to very small, phase II studies of low power. These demonstrate CIC has similar effectiveness and efficacy to FP and BUD (though equivalence is not certain) and findings regarding oral deposition and HPA suppression are inconclusive. There is no direct comparative evidence that CIC causes fewer side effects since none of the studies reported patient-based outcomes.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Chronic Disease; Fluticasone; Humans; Pregnenediones; Randomized Controlled Trials as Topic

Inhaled corticosteroids form the cornerstone of treatment for most patients with asthma. A range of compounds are available with a wide range of prescribable doses. In this overview, we summarize the findings from a number of Cochrane systematic reviews that have examined the relative benefits of different doses of beclometasone dipropionate, budesonide and fluticasone propionate when used to treat children and adults. The key findings are that all inhaled corticosteroids demonstrate a dose-response relationship for efficacy measures, but most of the benefit in mild-to-moderate severity disease is gained in the low-to-moderate dose range of each drug. In this group, high doses of fluticasone lead to small improvements in measures of control at the expense of a steep increase in the incidence of oral side-effects. In patients with severe disease who are dependent on oral steroids, there may be appreciable benefit in reducing oral steroids from very high compared with high doses of fluticasone.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Evidence-Based Medicine; Fluticasone; Forced Expiratory Volume; Humans; Peak Expiratory Flow Rate; Treatment Outcome

Although salmeterol (SLM)/fluticasone propionate (FP) combination has been widely used in the world, this is not yet available in Japan. The combination risk was concerned based on overseas reports about adrenal suppression with high dose FP or asthma exacerbation from undesirable administration of SLM without ICS. Therefore, in this article, it was reviewed the evidence of both efficacy profile and safety profile of the SLM/FP for the combination with FP and SLM, and it was concluded that safety concerns of SLM and FP are low and the benefits of SLM/FP combination exceed the risks, at least they are used properly. Since SLM/FP combination has synergic effect clinically, this will reduce high dose used FP and they also reduce using SLM without ICS. The compliance will be improved by the combination. To improve asthma control, Japanese clinicians expect to be available this combination soon.

Topics: Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Combinations; Fluticasone; Humans; Salmeterol Xinafoate

Topics: Adrenal Insufficiency; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Drug Administration Schedule; Fluticasone; Glucocorticoids; Humans

Clinical studies have shown that the combination of an inhaled corticosteroid (ICS) and a long-acting beta(2)-adrenoceptor agonist (LABA) for patients with asthma is more effective than the use of ICS alone in equivalent or higher doses, as well as the use of other combinations. However, the relatively higher acquisition costs for the combination therapy require assessment of the value of the incremental costs, especially from a societal perspective. This review provides an overall assessment of the cost effectiveness of ICS plus LABA combination therapy for asthma. A systematic literature research was conducted in MEDLINE to identify studies published between January 1994 and September 2005. Cost-effectiveness studies derived from 11 clinical studies were identified. The ICS plus LABA combination was compared with ICS alone in eight studies, ICS plus a leukotriene antagonist in two studies, and a leukotriene antagonist alone in one study. All studies focused on measuring direct medical costs in a total of six different healthcare systems, and three studies conducted sensitivity analyses, including productivity costs. Outcomes were measured in treatment success (changes in lung function), episode-free days, and symptom-free days by evaluating short-term follow-up. The combination of ICS and LABA was found to be more efficacious and cost effective compared with ICS alone or alternative combinations of controller medications. Further considerations for measuring long-term outcomes and dose-response relationships might be required to provide further evidence on the cost effectiveness of combination therapy with ICS plus LABA.

Topics: Acetates; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Clinical Trials as Topic; Cost-Benefit Analysis; Cyclopropanes; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Nebulizers and Vaporizers; Quinolines; Sulfides

Review the molecular mechanisms of action, efficacy, and potential side effects associated with inhaled corticosteroids (ICS) in children with persistent asthma.. Articles in English from MEDLINE. The following terms were used: corticosteroids, inhaled corticosteroids, asthma, children, beclomethasone, fluticasone, budesonide, ciclesonide, growth, adrenal insufficiency, bone mineral density, and oral candidiasis. Treatment guidelines, review articles, controlled trials, meta-analyses, and systematic reviews evaluating the efficacy and the adverse events of treatment with ICS were selected.. In vivo and in vitro studies show that the available ICS have different pharmacokinetic and pharmacodynamic properties that result in different action potentials. ICS also differ as to the systemic and local side effects. The bioavailability of these products is essential in order to determine the incidence of side effects. In general, ICS are capable of controlling asthma, reducing the number of exacerbations, medical consultations, hospitalizations, and the need of oral corticosteroid (applications) bursts. Improvement can also be seen in pulmonary function, especially in patients with recent onset asthma. The most documented adverse effect is transitory decrease of growth rate.. ICS are the main anti-inflammatory agent used to treat persistent asthma. When administered in low doses, they seem to be safe and effective. Patient monitoring allows for early detection of possible side effects associated with ICS.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biological Availability; Bone and Bones; Bone Density; Budesonide; Child; Child Development; Fluticasone; Humans; Pregnenediones; Treatment Outcome

The aim of this study was to examine the efficacy of fluticasone administered once daily compared to twice daily in asthma.. A meta-analysis was performed of randomized double-blind trials of at least 4 weeks duration that compared fluticasone administered once versus twice a day and presented data on at least one clinical outcome measure.. Six studies of 1517 children and adults with asthma met the inclusion criteria. Studies were predominantly in subjects with moderate asthma, treated with doses of fluticasone ranging from 200 to 500 microg per day. Twice-daily dosing was associated with significantly greater efficacy compared with once-daily dosing, for all outcome measures except night wakenings. The mean (95% CI) differences between twice and once-daily administration for FEV(1) and peak expiratory flow were 0.11 L (0.07-0.16) and 12.9 L/min (8.6-17.1), respectively. Twice-daily fluticasone was associated with significantly fewer withdrawals due to asthma than once-daily fluticasone, with an odds ratio of 0.44 (0.30-0.67).. The findings suggest that twice-daily administration of fluticasone will provide greater therapeutic benefit than a once-daily morning regimen.

Topics: Adolescent; Adult; Aged; Androstadienes; Asthma; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Fluticasone; Humans; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome

Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment of asthma.. 1. To assess efficacy and safety outcomes in studies that compared FP to placebo for treatment of chronic asthma.2. To explore the presence of a dose-response effect.. We searched the Cochrane Airways Group Trial Register (January 2004), reference lists of articles, contacted trialists and searched abstracts of major respiratory society meetings (1997-2004).. Randomised trials in children and adults comparing FP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. Two reviewers extracted data. Quantitative analyses where undertaken using RevMan Analyses 4.2.7.. Sixty eight studies met the inclusion criteria (11, 104 participants). Methodological quality was high. In non-oral steroid treated asthmatics with mild and moderate disease FP resulted in improvements from baseline compared with placebo across all dose ranges (100 to 1000 mcg/d) in FEV1 (between 0.13 to 0.45 litres); morning PEF (between 27 and 47 L/min); symptom scores (based on a standardised scale, between 0.5 and 0.85); reduction in rescue beta-2 agonist use (between 1.2 and 2.2 puffs/d). High dose FP reduced the number of patients dependent on prednisolone: FP 1000-1500 mcg/d Peto Odds Ratio 0.07 (95% CI 0.05 to 0.10). FP at all doses led to a greater likelihood of sore throat, hoarseness and oral Candidiasis, but 21 patients would need to be treated for one extra to develop Candidiasis (FP 500 mcg/day), whilst only three or four patients need to be treated to avoid one extra patient being withdrawn due to lack of efficacy at all doses of FP.. Doses of FP in the range 100-1000 mcg/d are effective. In most patients with mild-moderate asthma improvements with low dose FP are only a little less than those associated with high doses when compared with placebo. High dose FP appears to have worthwhile oral-corticosteroid reducing properties. FP use is accompanied by an increased likelihood of oropharyngeal side effects.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Dose-Response Relationship, Drug; Fluticasone; Humans; Randomized Controlled Trials as Topic

Inhaled fluticasone propionate (FP) is a high-potency inhaled corticosteroid used in the treatment of asthma.. 1. To assess the efficacy and safety outcomes of inhaled fluticasone at different nominal daily doses in the treatment of chronic asthma. 2. To test for the presence of a dose-response effect.. We searched the Cochrane Airways Group Trials Register (January 2005) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2004).. Randomised trials in children and adults comparing fluticasone at different nominal daily doses in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data. These were checked and verified by a second reviewer. Quantitative analyses where undertaken using RevMan (Analyses 1.0.2).. Forty-three studies (45 data sets with 8913 participants) met the inclusion criteria. Methodological quality was high. In asthmatics with mild to moderate disease who were not on oral steroids a dose-response effect was present with FP for change in morning peak expiratory flow (PEF). For low doses (100 versus 200 microg/day) the weighted mean difference (WMD) was 6.29 litres/min, 95% confidence interval (CI) 2.28 to 10.29. Comparing medium (400 to 500 microg/day) to low dose (200 microg/day) FP the WMD was 6.46 litres/min (95% CI 3.02 to 9.89); this effect was more pronounced in one trial with more severely asthmatic children. For FP 100 versus 400 to 500 microg/day the WMD was 8 litres/min (95% CI 1 to 15) and at high versus low doses (800 to 1000 versus 50 to 100 microg/d) the WMD was 22 litres/min (95% CI 15 to 29). When high and medium doses were compared there was no significant difference in the change in morning PEF: at 400 to 500 versus 800 to 1000 microg/day the WMD was 0.16 litres/min (95% CI 6.95 to 6.63). There was no dose-response effect on symptoms or rescue beta-2 agonist use. The likelihood of hoarseness and oral candidiasis was significantly greater for the higher doses (800 to 1000 microg/day). People with oral steroid-dependent asthma treated with FP (2000 microg/day) were significantly more likely to reduce oral prednisolone than those on 1000 to 1500 microg/day (Peto odds Ratio 2.8, 95% CI 1.3 to 6.3). The highest dose also allowed a significant reduction in daily oral prednisolone dose compared to 1000 to 1500 microg/day (WMD 2.0 mg/day, 95% CI 0.1 to 4.0 mg/day).. Effects of fluticasone are dose dependent but relatively small. At dose ratios of 1:2, there are significant differences in favour of the higher dose in morning peak flow across the low dose range. The clinical impact of these differences is open to interpretation. Patients with moderate disease achieve similar levels of asthma control on medium doses of fluticasone (400 to 500 microg/day) as they do on high doses (800 to 1000 microg/day). More work in severe asthma would help to confirm that doses of FP above 500 microg/day confer greater benefit in this subgroup than doses of around 200 microg/day. In oral corticosteroid-dependent asthmatics, reductions in prednisolone requirement may be gained with FP 2000 microg/day.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Chronic Disease; Fluticasone; Humans; Randomized Controlled Trials as Topic

Salmeterol/fluticasone propionate, administered twice daily via a multidose dry powder inhaler (Seretide/Advair Diskus), Seretide Accuhaler or metered-dose hydrofluoroalkane (chlorofluorocarbon-free) inhaler (Seretide Evohaler), is a combination of the long-acting beta(2)-adrenoceptor agonist (beta(2)-agonist) [LABA] salmeterol and the corticosteroid fluticasone propionate. Maintenance therapy with combined salmeterol/fluticasone propionate is at least as effective in improving lung function and symptoms and is as well tolerated in patients with asthma as concurrent salmeterol plus fluticasone propionate. In patients previously receiving as-required short-acting beta(2)-agonists (SABAs) or inhaled corticosteroids, salmeterol/fluticasone propionate was significantly more effective in providing asthma control than fluticasone propionate and in improving lung function and asthma symptoms than inhaled corticosteroids (at equivalent or higher dosages), salmeterol or montelukast (as monotherapy or in combination with fluticasone propionate). Salmeterol/fluticasone propionate was more effective in improving asthma symptoms than adjusted-dose budesonide/formoterol in patients with uncontrolled asthma despite treatment with inhaled corticosteroids with or without a LABA in a well designed 1-year study. In pharmacoeconomic analyses, salmeterol/fluticasone propionate compared favourably with inhaled corticosteroids and mono- or combination therapy with oral montelukast. Salmeterol/fluticasone propionate is, therefore, an effective, well tolerated and cost-effective option for the maintenance treatment of patients with asthma.

Topics: Acetates; Administration, Inhalation; Albuterol; Androstadienes; Asthma; Asthma, Exercise-Induced; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Economics, Pharmaceutical; Ethanolamines; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Quinolines; Salmeterol Xinafoate; Sulfides; Therapeutic Equivalency

There is uncertainty as to the dose of inhaled corticosteroids (ICS) at which to start concomitant long acting beta agonist (LABA) treatment in patients with asthma not adequately controlled by ICS alone.. A meta-analysis was carried out of randomised, double blind clinical trials that compared the efficacy of adding salmeterol to moderate doses of ICS (fluticasone propionate 200 mug/day or equivalent) with increasing the ICS dose by at least twofold in symptomatic adult patients with asthma. The main outcome measures were the number of subjects withdrawn from the study due to asthma and the number of subjects with at least one moderate or severe exacerbation.. Twelve studies with a total of 4576 subjects met the inclusion criteria for the analyses. The number of subjects withdrawn due to asthma and with at least one moderate or severe exacerbation was higher in the high dose ICS group (odds ratios 1.58, 95% CI 1.12 to 2.24 and 1.35, 95% CI 1.10 to 1.66, respectively). For the secondary outcome variables (forced expiratory volume in 1 second, morning and evening peak expiratory flow, and daytime beta agonist use) there was significantly greater benefit in the salmeterol group.. This meta-analysis shows that the addition of salmeterol to moderate doses of ICS (fluticasone 200 mug/day or equivalent) in patients with asthma symptomatic at that dose results in significantly greater clinical benefit than increasing the dose of ICS by twofold or more.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Treatment Outcome

Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment of asthma.. 1. To assess efficacy and safety outcomes in studies that compared FP to placebo for treatment of chronic asthma.2. To explore the presence of a dose-response effect.. We searched the Cochrane Airways Group Specialised Register (January 2005), reference lists of articles, contacted trialists and searched abstracts of major respiratory society meetings (1997-2004).. Randomised trials in children and adults comparing FP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. Two reviewers extracted data. Quantitative analyses were undertaken using RevMan 4.2. Seventy-five studies met the inclusion criteria (14,208 participants). Methodological quality was high. In non-oral steroid treated asthmatics with mild and moderate disease FP resulted in improvements from baseline compared with placebo across all dose ranges (100 to 1000 mcg/d) in FEV1 (between 0.13 to 0.45 litres); morning PEF (between 23 and 47 L/min); symptom scores (based on a standardised scale, between 0.5 and 0.85); reduction in rescue beta-2 agonist use (between 1.2 and 2.2 puffs/day). High dose FP increased the number of patients who could withdraw from prednisolone: FP 1000-1500 mcg/day Peto Odds Ratio 14.07 (95% CI 7.17 to 27.57). FP at all doses led to a greater likelihood of sore throat, hoarseness and oral Candidiasis. Twenty-one patients would need to be treated for one extra to develop Candidiasis (FP 500 mcg/day), whilst only three or four patients need to be treated to avoid one extra patient being withdrawn due to lack of efficacy at all doses of FP.. Doses of FP in the range 100-1000 mcg/day are effective. In most patients with mild-moderate asthma improvements with low dose FP are only a little less than those associated with high doses when compared with placebo. High dose FP appears to have worthwhile oral-corticosteroid reducing properties. FP use is accompanied by an increased likelihood of oropharyngeal side effects.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Dose-Response Relationship, Drug; Fluticasone; Humans; Randomized Controlled Trials as Topic

Cough in isolation of other clinical features is known as non-specific cough, which has been defined as non-productive cough in the absence of identifiable respiratory disease or any known aetiology. In children with non-specific cough the possibility of asthma being the underlying disorder is often raised (so called cough variant asthma). The proponents of cough variant asthma suggest a therapeutic trial of medications usually used to treat asthma.. To determine the efficacy of inhaled corticosteroids in non-specific cough in children over the age of two years.. Searches were conducted on Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Searches were current as of March 2004.. All randomised (randomised and quasi-randomised) controlled clinical trials in which an inhaled corticosteroid (beclomethasone (BDP), fluticasone (FP), triamcinalone (TAA) or any other corticosteroid) were given for cough in children over two years of age were included. Two review authors independently assessed articles for inclusion and methodological quality.. Data from trials was extracted by both review authors and entered into the Cochrane Collaboration software program RevMan Analyses 1.0.2.. Two trials met the inclusion criteria (123 participants). One compared inhaled beclomethasone dipropionate (400 micrograms per day) with placebo and the other compared fluticasone propionate (2 mg per day for 3 days followed by 1 mg per day for 11 days) with placebo. Both studies used metered dose inhalers via a spacer. With the lower dose of inhaled corticosteroid there was no significant difference between the beclomethasone and placebo groups. With the higher dose there was a significant improvement in nocturnal cough frequency after two weeks in children presenting with persistent nocturnal cough. However, a significant but smaller improvement was also seen with placebo.. In one study beclomethasone dipropionate (400 micrograms per day) was no different from placebo in reducing the frequency of cough measured objectively or scored subjectively. There might be a small improvement with very high-dose inhaled corticosteroid but the clinical impact of this is unlikely to beneficial.

Topics: Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Child, Preschool; Cough; Fluticasone; Humans; Randomized Controlled Trials as Topic

The relative efficacy of fluticasone (FP) and beclomethasone (BDP) propelled with CFCs has been well established. The potency of HFA-BDP is thought to have been improved with new propellant and some studies suggest that it may equipotent at half the dose of CFC propelled-BDP. There is a need to revisit this question in the light of a potentially more potent new non-CFC propellant.. To determine the relative efficacy of FP and HFA-propelled BDP in chronic asthma.. The Cochrane Airways Group Specialised Register was searched using pre-specified terms. Searches were current as of March 2005.. Randomised controlled trials were eligible for inclusion in the review. We compared either CFC or HFA-propelled FP with HFA-propelled BDP. We made a distinction between HFA-BDP and HFA-BDP extra fine, which dispenses smaller particles of drug, leading to different, usually more peripheral distribution in the airways. Any inhaler device was considered, and there was no restriction on studies with or without spacers. We included studies which assessed HFA-BDP given via either pMDI, breath-actuated MDI, or DPI.. Two reviewers independently assessed studies for inclusion in the review. Data were extracted and entered in to RevMan 4.2 using standard meta-analytical techniques with predefined criteria for exploring statistical heterogeneity.. Seven studies (1230 participants) met the inclusion criteria of the review. One study was conducted in children. Study reporting quality was fair, but all studies were of short duration (three to twelve weeks). Only studies assessing HFA-BDP extra fine in comparison with FP were identified. Lung function was not significantly different between extra fine BDP and FP when compared at the same dose in parallel studies, change in FEV1: 0.04 litres (95% CI -0.03 to 0.11 litres; three studies, 659 adults); change in am PEF: -0.69 litres (95% CI -11.21 to 9.83 litres; two studies, 364 adults). Individual studies reported non-significant findings in symptom scores and quality of life questionnaires. There was no significant difference between FP and HFA-BDP in the risk of study withdrawal, dysphonia or when data were reported as any adverse event.. There was no significant difference between FP and extra fine HFA-BDP on FEV(1) or peak flow at a dose ratio of 1:1. However, the number of studies and width of the confidence intervals in the analyses do not exclude a clinically meaningful difference between these two drugs. Difficulty in the successful manipulation of the devices studied may be a barrier to the widespread use of MDIs. One paediatric study was included in the review, so extrapolation of the findings of this review to children is limited. Further longer term studies in adults and children with moderate and severe asthma are required.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; Chronic Disease; Fluticasone; Humans; Randomized Controlled Trials as Topic

Medication for the treatment of asthma and chronic obstructive pulmonary disease should be given locally by inhalation. There is, however, no such thing as an ideal inhaler, or 'Idealhaler', which has all desired properties with no drawbacks. In this short review, we have compared the relative merits of the two most commonly used dry powder inhalers -- Turbuhaler and Diskus. Clinical effect is related to the amount of inhaled drug that reaches the lungs, and this in turn depends on the amount of fine particles generated at inhalation. Turbuhaler is more than twice as effective as Diskus at generating fine particles, and the higher lung deposition with Turbuhaler is accompanied by a lower variability in lung deposition. Compared with Diskus, the lung deposition with Turbuhaler is affected less by factors such as humidity.

Topics: Administration, Inhalation; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Fluticasone; Humans; Nebulizers and Vaporizers; Particle Size; Pulmonary Disease, Chronic Obstructive

Different international guidelines recommend the early introduction of inhaled corticosteroids (ICS) and their regular use to gain clinical and functional control of persistent asthma. There is now evidence that the starting dose of all ICS is lower than previously regarded. Initial moderate ICS doses appear to be more effective than an initial low ICS dose. The lowest effective dose should always be seeked by a step-down procedure. More than 90% of benefit is achieved by approximately a daily regular dose of 200 microg of fluticasone or 400 microg of beclomethasone or budesonide. The beneficial effects of increasing the dose of ICS alone appear to be modest in most cases. Intermittent ICS therapy has been successfully used in the long term treatment of mild asthma. In general, twice-daily administration of ICS provides greater therapeutic benefit than a once-daily regimen in moderate asthma. When asthma control has been obtained, a once-daily regimen can be tried. In clinical practice, this has the potential advantage of increasing patients' compliance. Chlorofluorocarbon-free formulations of old ICS have also remarkably improved their clinical efficacy mainly through an increased peripheral deposition pattern. Despite some limitations due to poor response in neutrophilic asthma and to potential systemic side effects, ICS will certainly be the cornerstone of asthma therapy even the next future.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Fluticasone; Humans

A study was undertaken to examine the dose-response relation of inhaled fluticasone in adolescents and adults with asthma.. A meta-analysis was carried out of randomised clinical trials that presented data on at least one outcome measure of asthma and that used at least two doses of fluticasone given twice daily. The main outcome measures were forced expiratory volume in 1 second (FEV1), morning peak expiratory flow (amPEF), beta agonist use, and withdrawals due to exacerbations of asthma.. Seven studies of 2431 adolescents and adults with moderate to severe asthma met the inclusion criteria for the meta-analysis. Four studies examined a dose of >500 microg/day. For all outcome measures there were no statistically significant differences between a dose of 200 v 500 microg/day, 500 v 1000 microg/day, and 200 v > or =500 microg/day, although the point estimates favoured the higher doses. The mean improvement for FEV1 and amPEF resulting from an increase in dose from 200 to > or =500 microg/day was 0.07 l (95% CI -0.01 to 0.14) and 5.9 l/min (95% CI -3.0 to 15.3), respectively. The odds ratio for withdrawals with 200 microg/day compared with > or =500 microg/day was 1.27 (95% CI 0.78 to 2.07).. In adolescents and adults with asthma, most of the therapeutic benefit of fluticasone is achieved with a total daily dose of 200 microg/day with minimal further clinical benefit achieved with higher doses. This conclusion is qualified by the recognition that there is considerable individual variability in the response to inhaled corticosteroids in asthma, which would suggest that some patients may obtain a greater clinical benefit at higher doses.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Dose-Response Relationship, Drug; Fluticasone; Forced Expiratory Volume; Humans; Middle Aged; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Delayed-Action Preparations; Down-Regulation; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Salmeterol Xinafoate; Treatment Outcome

Inhaled corticosteroids (ICS) are the mainstay of asthma therapy. Although compliance to this type of medication is often suboptimal and once-daily dosing can help to improve adherence to the treatment, the clinical implications of such a mode of administration should be determined.. This review summarizes the recent studies on comparative efficacy of once-versus twice-daily administration of ICS, in light of previous reports.. Although twice-daily administration of ICS is often better to optimize asthma parameters, in many patients, asthma can be sufficiently controlled by a once-daily regimen of most ICS. An increased frequency of dosing seems preferable if asthma becomes uncontrolled or is severe, although this requires further study. A therapeutic trial should, however, be done to ensure that asthma control is adequate. Comparative long-term effects of such a strategy on inflammatory and remodeling parameters remain to be determined, as does the proportion of patients who can adequately control their asthma with once-daily administration of the various ICS available.

Topics: Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Fluticasone; Glucocorticoids; Humans; Mometasone Furoate; Pregnadienediols; Treatment Outcome

The impact of long-term inhaled corticosteroid (ICS) therapy on bone mineral density (BMD) is poorly understood.. To evaluate the impact of long-term ICS use on BMD.. Random-effects meta-analysis. Published and unpublished literature were identified by searches of MEDLINE and EMBASE databases and consultation with experts. Studies reporting BMD among adult asthma and chronic obstructive pulmonary disease (COPD) patients using ICS and non-ICS controls were identified. Studies selected for review included at least 1 year of follow-up. Two independent reviewers evaluated studies; data from those meeting specified inclusion criteria were abstracted for inclusion in the meta-analysis.. Fourteen (5.3%) of 266 reviewed studies met specified inclusion criteria. Sufficient data were available to perform meta-analysis on 3 measures for ICS-using patients (lumbar, femoral neck, and major trochanter BMD) and 1 measure (lumbar BMD) for non-ICS-using controls. Using current National Asthma Education and Prevention Program definitions, the majority of studies (12 of 14) included patients receiving moderate to high doses of ICSs. Among ICS users, annual changes from baseline in lumbar, femoral neck, and major trochanter BMD (-0.23%, -0.17%, and +1.46%, respectively) were not statistically significant. Mean changes in lumbar BMD were also not significantly different from controls (-0.02%). Further, annual changes in lumbar BMD were not statistically significant for subgroups of patients with asthma or COPD.. Long-term use of ICSs in patients with asthma or COPD was not associated with significant changes in BMD.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bone Density; Budesonide; Fluticasone; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Triamcinolone Acetonide

Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma, Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays.. To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma.. We searched the Cochrane Airways Group trial register (January 2003) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2003).. Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data. Quantitative analyses were undertaken using RevMan analyses 1.0.1.. 48 studies (11,479 participants) met the inclusion criteria. Methodological quality was variable. When compared at a FP:BUD/BDP dose ratio of 1:2, fluticasone produced a significantly greater FEV1 (Weighted Mean Difference (WMD) 0.11 litres, 95% Confidence Interval (CI) 0.01 to 0.20 litres), morning PEF (WMD 13 L/min, 95%CI 5 to 22 L/min) and evening PEF (WMD 11 L/min, 95%CI 1 to 20 L/min). This applied to all drug doses, age groups, and delivery devices, although subgroup analyses suggested that the relative benefit of FP may be greater in more severe patients treated with higher doses of inhaled corticosteroid. No difference between fluticasone and beclomethasone or budesonide were seen for trial withdrawals (Peto OR 0.76, 95%CI 0.53 to 1.09). Symptoms and rescue medication use were widely reported but few trials provided sufficient data for analysis. A higher likelihood of pharyngitis (Peto Odds Ratio 2.16; 95% CI 1.43 to 3.24) was apparent when patients were treated with fluticasone at twice the dose of BDP/BUD, although there was unexplained heterogeneity in this effect between trials. There was no difference in the likelihood of oral Candidiasis. Plasma cortisol and 24 hour urinary cortisol were measured frequently but data presentation was limited.. Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing side-effects when given at the same daily dose.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Randomized Controlled Trials as Topic

Inhaled corticosteroids (ICS) form the basis of maintenance therapy in asthma and their efficacy is well established. However, the optimal starting dose of ICS is not clearly established. Recent reviews demonstrate a relatively flat efficacy curve for ICS and increasing side effects with increasing ICS doses. High doses are frequently prescribed and there are now reports of significant side effects occurring with high dose ICS use. These issues demonstrate the need to establish the optimal starting dose of ICS in asthma.. To establish the optimal starting dose of ICS by evaluating the efficacy of initial high dose ICS with low dose ICS in subjects with asthma, not currently on ICS.. We searched the Cochrane Airways Group trials register and reference lists of articles. Date of last search: January 2003. Randomised controlled trials of two different doses of the same ICS in adults and children with asthma with no concomitant ICS or OCS.. Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for confirmation. Trials were analysed according to the following ICS dose comparisons: step down vs constant dose ICS (n=7); high vs moderate (n=11); high vs low (n=9); moderate vs low (n=11); fold change in dose (all studies).. 31 papers reporting the results of 26 trials were included in the review. For studies that compared a step down approach to a constant moderate/low ICS dose, there were no significant differences in lung function, symptoms, rescue medications or asthma control between the two treatment approaches. Significant but clinically small improvements in percent predicted FEV(1) ( WMD 5.32, 95% CI 0.65 to 9.99) and non significant improvements in the change in morning PEF were found for high dose ICS compared to moderate dose ICS. There were no significant differences in efficacy between high and low dose ICS. For moderate dose ICS, compared to low dose ICS, there were significant improvements in the change in morning PEF l/min from baseline (WMD 11.14, 95% CI 1.34 to 20.93) and nocturnal symptoms (SMD -0.29, 95% CI -0.53 to -0.06 ). Commencing ICS at double or quadruple a base moderate or low dose had no greater effect than commencing with the base dose. Several studies reported greater improvement in airway hyperresponsiveness for high dose ICS.. For patients with asthma who require ICS, commencing with a moderate dose ICS is equivalent to commencing with a high dose ICS and down-titrating. The small significant benefits of commencing with a high ICS dose are not of sufficient clinical benefit to warrant its use when compared to moderate or low dose ICS. Initial moderate ICS dose appears to be more effective than initial low ICS dose. High dose ICS may be more effective than moderate or low dose ICS for airway hyperresponsiveness. There is no benefit in doubling or quadrupling ICS in subjects with stable asthma.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Fluticasone; Humans; Randomized Controlled Trials as Topic

In 1999, a robust dose-finding study showed that the chlorofluorocarbon (CFC) -free formulation of beclometasone dipropionate (BDP), QVAR (hydrofluoroalkane-134a BDP), produced equivalent asthma control to CFC-BDP at approximately half the daily dose in adults. Since then, a wealth of clinical and pharmaco-vigilance studies have been undertaken to confirm these results and establish dose-potency ratios with other inhaled corticosteroids (ICS). This review summarises the results of studies performed by the manufacturer that have been published since the last comprehensive review of the efficacy and safety of QVAR in 2000. Long-term comparisons with CFC-BDP have confirmed the durability of the 2:1 daily dosing ratio of CFC-BDP:QVAR in adults. Clinical comparisons with other ICS in both symptomatic and asymptomatic patients have established dose-potency ratios of 2: 1 for budesonide:QVAR and 1:1 for fluticasone:QVAR. Furthermore, QVAR has been associated with benefits on asthma symptomatology and quality of life, compared with other ICS that probably arises from its peripheral deposition in the lung.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Multicenter Studies as Topic; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Treatment Outcome; Vital Capacity

To examine the dose-response relation of inhaled fluticasone for both efficacy and adrenal function in children with asthma.. Systematic review of double blind randomised dose-response studies of fluticasone in children of at least 4 weeks duration.. FEV1, morning peak expiratory flow, night awakenings, beta agonist use, major exacerbations, 12 or 24 hour urinary cortisol, peak plasma cortisol post-stimulation.. Seven studies of 1733 children with asthma met the inclusion criteria for efficacy. The dose-response curve for each efficacy outcome measure suggested that the response began to plateau between 100 and 200 microg per day with additional efficacy at the 400 microg per day dose shown in one study of severe asthmatics. Five studies of 1096 children with asthma met the inclusion criteria for assessment of adrenal function. The largest placebo controlled study of 437 children reported no difference in 24 hour urinary cortisol between placebo and fluticasone at doses of 100 and 200 microg per day. The non-placebo controlled study of 528 children reported significant suppression of overnight urinary cortisol levels with fluticasone at 400 compared with 200 microg per day.. There is insufficient data to determine the dose-response of fluticasone in children at doses >400 microg per day. The dose-response curve for fluticasone appears to plateau between 100 and 200 microg per day for efficacy. There was additional efficacy at the 400 microg per day dose in children with severe asthma; however there was evidence of adrenal suppression at this dose.

Topics: Administration, Inhalation; Androstadienes; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Humans; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Treatment Outcome

The introduction of inhaled corticosteroids (ICS) has been a milestone in asthma therapy. According to current guidelines ICS are the first line drug in chronic anti-inflammatory therapy. The purpose of first part of this publication is to present updated knowledge on mechanisms of anti-inflammatory action as well as some pharmacokinetics and pharmacodynamics data about commonly used ICS, especially fluticasone propionate (FP) and two others: budesonide (BUD), beclomethasone dipropionate (BDP). Some differences between mentioned drugs have been found concerning systemic activity and safety of therapy. Fluticasone propionate is twice as active as the BUD and BDP. First results of therapy are seen 1-2 week after administration. Fluticasone propionate, more lipophilic than other steroids, has also high glucocorticoid receptor affinity and specificity, high topical anti-inflammatory activity and low systemic bioavailability. Systemic availability of FP depends on absorption from respiratory system. Oral bioavailability can be neglected because of almost total inactivation in liver during first pass. Fluticasone propionate has some features of dissociated steroids which means predominance of transrepression over transactivation--beneficial from safety point of view. Clinical efficacy of FP in chronic asthma therapy in children was confirmed in many studies. It significantly reduces the symptoms and exacerbations of asthma. There is a close correlation between FP use and lung function tests. The therapy with FP decreases bronchial hyperreactivity and the use of systemic steroids and rescue medication. The beneficial action of fluticasone propionate in asthma is due its anti-inflammatory properties within the airways (decreasing levels of direct and indirect markers of airways inflammations are observed).

Topics: Administration, Inhalation; Adolescent; Age Factors; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biological Availability; Budesonide; Child; Child, Preschool; Drug Administration Schedule; Female; Fluticasone; Glucocorticoids; Humans; Infant; Infant, Newborn; Male; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Treatment Outcome

Inhaled administration of glucocorticoid doesn't mean lack of systemic effects of drug. Bioavailability of steroid depends on oral absorption and absorption from respiratory system. In case of fluticasone propionate (FP) swallowed dose can be neglected because almost total (>99%) inactivation in liver during first pass. In second part of paper the most important safety parameters of therapy with FP are discussed, it means; influence on hypothalamic-pituitary-adrenal axis, growth and bone metabolism. Interpretation of potential side effects should differentiate between abnormal value of laboratory test and clinically important symptoms. Adrenal suppression depends on dose of FP and was found even after low dose (about 200 microg per day), but clinical value of this findings is unknown. Prolonged administration of high doses can suppress hypothalamic-pituitary-adrenal axis; exceptionally, it can induce adrenal insufficiency. Recommended doses of FP given 1 to 2 years doesn't cause growth retardation. Long term studies on influence of drug on final height are needed. FP as other inhaled corticosteroids, may transiently alter bone metabolism. Till now there are no evidences that this drug, when prescribed appropriately in standard doses for asthma control, may decrease the bone mineral density or induce osteoporosis and may increase the risk of bone fractures in asthmatic children. Effective asthma control achieved with FP therapy permits normal activity and development of asthmatic children which prevails over exceptionally noticed side effects.

Topics: Administration, Inhalation; Adolescent; Age Factors; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bone Density; Child; Child, Preschool; Drug Administration Schedule; Female; Fluticasone; Humans; Hypothalamo-Hypophyseal System; Infant; Infant, Newborn; Male; Osteoporosis; Pituitary-Adrenal System; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome

Topics: Administration, Inhalation; Adult; Androstadienes; Antiviral Agents; Asthma; Biological Availability; Cushing Syndrome; Cytochrome P-450 Enzyme Inhibitors; Drug Therapy, Combination; Fluticasone; Glucocorticoids; HIV Infections; Humans; Lopinavir; Male; Pyrimidinones; Ritonavir

Deleterious effect of oral corticosteroids on bone has been well documented, whereas this remains debated for inhaled ones (ICS). Our objectives were to analyze the effects of ICS on bone mineral density, fracture risk and bone markers. We performed an exhaustive systematic research of all controlled trials potentially containing pertinent data, peer-reviewed by a dedicated WHO expert group, and comprehensive meta-analyses of the data. Inclusion criteria were ICS, and BMD/markers/fractures in asthma/chronic obstructive pulmonary diseases (COPD) and healthy patients. Analyses were performed in a conservative fashion using professional dedicated softwares and stratified by outcome, study design and ICS type. Results were expressed as standardized mean difference/effect size (ES), relative risk (RR) or odds ratio (OR), depending on study design and outcome units. Publication bias was investigated. Twenty-three trials were reviewed; 11 papers fit the inclusion criteria and were assessed for the main analysis. Quality scores for the randomized controlled trials (RCTs) were 80%, 71% for the prospective cohort studies, and 78% for the retrospective cohort and cross-sectional studies. We globally assessed ICS effects on BMD and found deleterious effects: ES=0.61 ( p=0.001) for healthy subjects, and ES=0.27 ( p<0.001) for asthma/COPD patients. For these patients, this effect was 0.21 ( p<0.01) at the lumbar spine, and 0.26 ( p<0.001) at the hip or femoral neck. A single study evaluated the impact of ICS on hip fracture and reported an increased OR of 1.6 (1.24; 2.03). Lumbar fracture rate differences did not reach the level of statistical significance: 1.87 (0.5; 6.94). Osteocalcin and PICP were decreased and ICTP, pyridinoline and deoxypyridinoline levels were not significantly affected. Budesonide (BUD) appeared to be the ICS inducing the less deleterious effects on bone, followed by beclomethasone dipropionate (BDP) and triamcinolone (TRI). Publication bias investigation provided non-significant results. In our meta-analyses, BUD at a mean daily dose (SD) of 686 microg (158 microg), BDP at 703 microg (123 microg) and TRI at 1,000 microg (282 microg) were found to affect bone mineral density and markers in patients suffering from the two major respiratory diseases. These findings could have practical implication in the long-term management of asthmatic and COPD patients.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bone and Bones; Bone Density; Budesonide; Fluticasone; Fractures, Bone; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Triamcinolone Acetonide

Fear of growth retardation may account for the underuse of inhaled corticosteroids in children with asthma, despite compelling evidence of their effectiveness. This fear may be reduced with newer agents with lower oral bioavailability if their theoretical advantage of fewer systemic adverse effects than the standard treatment of inhaled beclometasone is realized in practice. This review aims to determine if one of the newer agents, inhaled fluticasone, has less effect on the growth of pre-pubertal asthmatic children than inhaled beclometasone. The outcome measure was growth velocity. Two double blind, randomized controlled trials were identified. In one of the studies the mean growth velocity in the fluticasone group was 0.7 cm/year greater than in the beclometasone group. In the second, smaller study the mean growth velocity in the fluticasone group was 0.8 cm/year greater. There is therefore some evidence that fluticasone has less (if any) adverse effect on growth.

Topics: Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Fluticasone; Growth Disorders; Humans

The coadministration of long-acting inhaled beta(2)-agonists and inhaled corticosteroids is the most effective treatment for persistent asthma.. This meta-analysis aimed to determine the efficacy of fluticasone propionate and salmeterol inhaled from a single inhaler (combination therapy) or from separate inhalers (concurrent therapy).. Four similarly designed double-blind studies individually confirmed equivalence between combination and concurrent therapy on the basis of the primary efficacy measure (morning peak expiratory flow [PEF]). Each study showed a consistent trend in favor of combination therapy. Individual patient data from these studies were combined to provide overall estimates of treatment effect for morning PEF and other efficacy measures.. Fixed-effects meta-analysis showed a significant advantage for combination therapy compared with concurrent therapy in morning PEF (mean difference between groups in change from baseline over 12 weeks of 5.4 L/min; P =.006; 95% CI = 1.5-9.2). Logistic regression analysis showed that the odds of achieving a greater than 15 or greater than 30 L/min improvement with combination therapy were increased by approximately 40% compared with those after concurrent therapy (15 L/min: odds ratio = 1.42, P =.008, 95% CI = 1.1-1.8; 30 L/min: odds ratio = 1.40, P =.006, 95% CI = 1.1-1.8), representing an additional 7% to 9% and 5% to 14% more patients, respectively, on combination therapy responding compared with those on concurrent therapy.. The meta-analysis indicates that the fluticasone propionate plus salmeterol combination offers the potential for increased clinical efficacy over concurrent use of the same doses of the same 2 drugs. After administration from a single inhaler, fluticasone propionate and salmeterol might codeposit in the airways. It is hypothesized that this codeposition offers an increased opportunity for synergistic interaction to occur.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Asthma; Drug Synergism; Drug Therapy, Combination; Fluticasone; Humans; Lung; Nebulizers and Vaporizers; Salmeterol Xinafoate

Epidemiological studies showed that bronchial asthma is one of the most common diseases which can complicate pregnancy (1-7%). In about 0.05-2% of the cases, asthma occurs as a life-threatening event. In the common medical practice a waiting strategy or, even, the complete refusal for drug therapies are frequently observed. This is justified by the fear of the possible adverse effects of drugs on developing fetus. On the contrary, several studies have demonstrated that severe and uncontrolled asthma may produce serious maternal and fetal complications, such as gestational hypertension and eclampsia, fetal hypoxemia and an increased risk of perinatal death. Therefore, all pregnant women suffering from bronchial asthma should be considered as potentially at high risk of complications and adequately treated. Since asthma is a chronic disease with acute exacerbations, a continuous treatment is mandatory to control symptoms, to prevent acute episodes and to reduce the degree of airway inflammation. The global strategy for asthma management in pregnancy includes five main topics: (1) objective evaluation of maternal/ fetal clinical conditions; (2) avoidance/control of triggering factors; (3) pharmacological treatment; (4) educational support; (5) psychological support. As far as drug therapy is concerned, the International Guidelines and Recommendations suggest that the general strategy does not differ significantly from management outside pregnancy. We herein review and discuss the available data and the criteria for the management of asthma in pregnant patients.

Topics: Adrenergic beta-Agonists; Adult; Androstadienes; Anesthesia, Local; Anesthesia, Obstetrical; Asthma; Bronchodilator Agents; Chronic Disease; Contraindications; Cromolyn Sodium; Female; Fluticasone; Glucocorticoids; Histamine H1 Antagonists; Humans; Immunotherapy; Obstetric Labor Complications; Oxytocics; Patient Education as Topic; Pregnancy; Pregnancy Complications; Theophylline

Asthma guidelines recommend an inhaled corticosteroid plus a long-acting inhaled beta(2)-agonist (beta(2)-adrenoceptor agonist) as the preferred maintenance therapy for moderate and severe persistent asthma. Advair/Seretide Diskus also registered as Accuhaler is fixed-dose salmeterol (a long-acting inhaled beta(2)-agonist) and fluticasone propionate (a corticosteroid) administered via a single powder inhalation device. The clinical effectiveness of salmeterol/fluticasone propionate in patients with persistent asthma symptoms has been established in comparative clinical trials. Pharmacoeconomic analyses, based on data from these clinical trials, have been conducted from a healthcare payer perspective in various countries. In patients with asthma not controlled with inhaled corticosteroids, salmeterol/fluticasone propionate was associated with more favourable (lower) cost-effectiveness ratios than fluticasone propionate monotherapy, oral montelukast plus inhaled fluticasone propionate, inhaled budesonide, and inhaled formoterol plus budesonide. As the initial maintenance therapy in patients with persistent asthma symptoms while receiving short-acting beta(2)-agonists alone, salmeterol/fluticasone propionate was cost effective relative to montelukast monotherapy. Although the total cost of asthma management tended to be slightly higher with salmeterol/fluticasone propionate than with fluticasone propionate or montelukast monotherapy, salmeterol/fluticasone propionate consistently had a more favourable cost-effectiveness ratio in terms of per successfully treated week or symptom-free day and/or was associated with small incremental costs to achieve significant additional clinical benefits. In clinical practice, salmeterol plus fluticasone propionate was associated with lower asthma-related costs than treatment with other maintenance therapies.In patients with asthma symptoms despite treatment with inhaled corticosteroids, salmeterol/fluticasone propionate produced clinically meaningful improvements in overall Asthma Quality of Life Questionnaire (AQLQ) scores relative to salmeterol or placebo monotherapy, in emotional function domain scores relative to fluticasone propionate or budesonide, and in asthma symptoms domain scores relative to budesonide. In patients with persistent asthma symptoms while receiving short-acting beta(2)-agonists alone, salmeterol/fluticasone propionate produced clinically meaningful improvements in overall AQLQ scores compared with f. Pharmacoeconomic analyses indicate that salmeterol/fluticasone propionate administered via a single inhaler represents a cost-effective treatment option (relative to fluticasone propionate at the same nominal dosage, budesonide, formoterol plus budesonide and montelukast plus fluticasone propionate) in patients with asthma not controlled with inhaled corticosteroid therapy. In patients with asthma not controlled with short-acting beta(2)-agonists alone, salmeterol/fluticasone propionate is a cost effective treatment relative to monotherapy with montelukast. Importantly, salmeterol/fluticasone propionate is also associated with improvements in health-related quality of life.

Topics: Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Cost-Benefit Analysis; Drug Combinations; Fluticasone; Humans; Salmeterol Xinafoate

Classification of severity of bronchial asthma is a basic point for therapeutic management in adults. In the paper definitions of severe and difficult asthma are presented. The therapeutic possibilities are pointed according to new guidelines published in the recent period and own Author's clinical experience.

Topics: Adult; Androstadienes; Asthma; Bronchodilator Agents; Fluticasone; Humans; Severity of Illness Index

Inflammation is the pathogenetic basis of many airway diseases like asthma and rhinitis. This provides the rationale for a therapy with antiinflammatory drugs like inhaled corticosteroids (ICS), which are able to suppress the underlying pathologic processes, ensuring an effective control of the disease and improving patients's quality of life. Within ICS, fluticasone is endowed of a potent antiinflammatory activity, due to its high affinity for the the glucocorticoid receptor (allowing the use of 50% of the dose of other ICS) and of a negligible oral bioavailability (<1%), indicating a low potential for systemic exposure. Due to its high therapeutical index, fluticasone can be used in the management of severe asthma or other airway diseases at doses devoid of relevant unwanted systemic effects. Scientific literature has broadly demonstrated its efficacy and safety, even at high doses and in the long term use.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Clinical Trials as Topic; Fluticasone; Humans; Rhinitis

The worldwide prevalence of asthma is increasing by approximately 50% per decade. Budesonide is one of several inhaled corticosteroids available for the treatment of asthma and has been extensively evaluated in clinical trials.. This article reviews the published literature on the efficacy of budesonide in the management of adult and pediatric patients with moderate to severe asthma and compares budesonide with other inhaled corticosteroids and nonsteroidal treatment options.. All controlled, randomized studies in patients with moderate or severe asthma were considered for inclusion. Relevant studies were identified through a MEDLINE search of the period from 1980 to 2000 using the terms budesonide plus efficacy, with or without the termsfluticasone, mometasone, and beclomethasone. The manufacturer's reference database was used to identify additional publications.. Budesonide is associated with a dose-response effect in adults and children with moderate to severe asthma. The data on budesonide are in line with the current recommendation for a high starting dose of inhaled corticosteroid (800 microg/d), followed by downward titration to the minimal effective dose. Budesonide administered by Turbuhaler (AstraZeneca Pharmaceuticals LP, Wilmington, Del) dry-powder inhaler (DPI) was effective at a significantly lower dose than beclomethasone dipropionate (BDP) administered by pressurized metered-dose inhaler (pMDI) (P = 0.009), whereas its efficacy was similar to that of BDP delivered by hydrofluoroalkane pMDI and that of fluticasone propionate administered by DPI. Inhaled budesonide therapy was shown to be oral corticosteroid sparing in patients with severe asthma, thus reducing the total corticosteroid dose and the risk of systemic side effects. Pulmicort Respules (AstraZeneca), a nebulized formulation, was effective in the treatment of moderate to severe asthma in patients aged > or =12 months.. Once- or twice-daily administration of budesonide delivered via the Turbuhaler and Pulmicort Respules systems has been shown to be well tolerated and efficacious in populations with moderate to severe asthma.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Fluticasone; Humans; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome

To evaluate the relative clinical superiority of increasing the dose of fluticasone propionate versus the addition of salmeterol to low-dose fluticasone propionate for long-term asthma control.. Literature was identified by a MEDLINE search (1966-October 2002). Key search terms included asthma, inhalation, corticosteroid, beta-adrenergic agonist, and combination drug therapy.. Current guidelines for long-term control of asthma include treatment with either inhaled corticosteroids (medium dose) or inhaled corticosteroids (low to medium dose) in combination with a long-acting bronchodilator. Previous studies evaluating salmeterol or formoterol combination therapy with beclomethasone or budesonide have generally produced superior results compared with increasing the dose of the inhaled corticosteroid. Four recent controlled clinical trials have compared the clinical utility of fluticasone propionate monotherapy versus salmeterol/low-dose fluticasone propionate for long-term asthma control in patients with moderate to severe persistent asthma. Based on spirometry data, rescue albuterol use, and symptom scores, the addition of salmeterol to low-dose fluticasone propionate was superior to increasing the dose of fluticasone propionate.. Based on improvements in forced expiratory volume in 1 second, peak expiratory flow, and symptom control, the addition of salmeterol to low-dose fluticasone propionate provides better control of asthma than increasing the dose of fluticasone propionate.

Topics: Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Clinical Trials as Topic; Fluticasone; Humans; Salmeterol Xinafoate

Inhalation is the preferred route for the application of drugs in the management of airway diseases. Therefore it was aimed at developing drugs suitable for inhalation. An important step was the introduction of the short- and long-acting beta 2-agonists and of a new generation of anticholinergics with longer duration of action. Most important was the development of inhaled glucocorticoids allowing good asthma control without relevant side effects even in a long run. Furthermore, the devices for drug application have been improved, and CFCs were substituted by HFAs.

Topics: Administration, Inhalation; Administration, Topical; Adrenergic beta-Agonists; Aerosols; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Cholinergic Antagonists; Clinical Trials as Topic; Drug Combinations; Fluticasone; Glucocorticoids; Humans; Ipratropium; Patient Compliance; Placebos; Powders; Salmeterol Xinafoate; Scopolamine Derivatives; Time Factors; Tiotropium Bromide

The current concept of asthma pathogenesis is that a characteristic chronic inflammatory process involving the airway wall causes the development of airflow limitation and increased responsiveness, thereby predisposing the airways to narrow in response to a variety of specific (allergic) or unspecific stimuli. Medications for asthma are used to reverse and prevent symptoms and airflow limitation and include controllers and relievers. The major advantage of delivering drugs directly into the airways via inhalation is that high concentrations can be delivered more effectively to the airways, and systemic side effects are avoided or minimized. Bronchodilators with or without anti-inflammatory substances are used as basic therapeutic approach in these patients. The stepwise approach to therapy recommends that the number/type and frequency of medications are increased with increasing asthma severity by adding systemic medications to existing inhalation therapy (step III-IV in asthma management guidelines). Combination therapy using a long acting beta 2-agonist and a glucocorticosteroid resulted in higher lung function improvement, and was superior in reduction of exacerbation rates compared with an inhaled glucocorticosteroid alone. Hence, the development of a fixed combination containing both substances in one device is a logic consequence, and thus, simplifying asthma therapy.

Topics: Administration, Inhalation; Administration, Topical; Adrenergic beta-Agonists; Adult; Albuterol; Allergens; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Drug Combinations; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Patient Compliance; Pregnancy; Pregnancy Complications; Salmeterol Xinafoate

A small effect (1 cm) of inhaled corticosteroids (ICS) on the 1-year growth of asthmatic children was observed in studies published during the 1990s. A high volume of literature published during the past year confirmed mild growth suppression at one year, but provided information on the effects of longer-term treatment. These developments are important, since the effect was previously unknown and the findings have major implications for asthma caregivers and the communication that they have with asthmatic children and their parents. The possibility that this is an idiosyncratic effect received conflicting support. These studies collectively provide support for ICS use and ease the minds of caregivers, parents, and children. The risk of growth retardation can be lessened and managed by the employment of several simple strategies: (1) monitor growth; (2) use the minimal effective dose; (3) optimize steroid-sparing strategies (smoke and allergen environmental controls, vaccinate for influenza, diagnose and treat rhinitis, sinusitis, and gastroesophageal reflux disease, use add-on therapy with a second controller rather than doubling the ICS dose if control is inadequate); and (4) use spacing devices (for pressurized metered-dose inhalers) and mouth rinsing. Open and accurate communication with patients and parents about this possible effect is essential to minimize nonadherence. Ultimately, no child whose disease severity warrants ICS therapy should be denied the tremendous benefits that this therapy can provide because of relatively minor concerns about growth effects.

Topics: Androstadienes; Asthma; Body Height; Budesonide; Child; Fluticasone; Glucocorticoids; Humans; Respiratory Function Tests

Long-acting inhaled beta2-agonists and inhaled corticosteroids are classes of drugs with different mechanisms of action that are commonly used to provide effective long-term control of persistent asthma. Scientific and clinical data support the complementary mechanisms of action of the inhaled corticosteroids and the long-acting beta2-agonists in achieving a superior level of asthma control. In addition, evidence supports significant reductions in exacerbations and effective control of airway inflammation with an inhaled corticosteroid and a long-acting beta2-agonist versus higher dosages of inhaled corticosteroids or combinations of other therapeutic agents with an inhaled corticosteroid. Finally, there are distinct economic advantages to combining an inhaled corticosteroid and a long-acting beta2-agonist in the treatment of asthma relative to other treatment regimens.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Cost-Benefit Analysis; Drug Therapy, Combination; Fluticasone; Humans; Leukotriene Antagonists; Salmeterol Xinafoate; Triamcinolone Acetonide

Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma, Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays.. To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma.. We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997-1999).. Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data. Quantitative analyses where undertaken using Review Manager 4.0.3 with Metaview 3.1.. 42 studies (>10,000 patients) met the inclusion criteria. Methodological quality was variable. When compared at a FP:BUD/BDP dose ratio of 1:2, fluticasone produced a significantly greater FEV1 (Weighted Mean Difference (WMD) 0.11 litres, 95% Confidence Interval (CI) 0.01, 0.20 litres), morning PEF (WMD 13 L/min, 95%CI 5, 22 L/min) and evening PEF (WMD 11 L/min, 95%CI 1, 20 L/min). This applied to all drug doses, age groups, and delivery devices, although subgroup analyses suggested that the relative benefit of FP may be greater in more severe patients treated with higher doses of inhaled corticosteroid. No difference between fluticasone and beclomethasone or budesonide were seen for trial withdrawals (Peto OR 0.77, 95%CI 0.54, 1.10). Symptoms and rescue medication use were widely reported but few trials provided sufficient data for analysis. A higher likelihood of pharyngitis (Peto Odds Ratio 2.16; 95% CI 1.42, 3.28) was apparent when patients were treated with fluticasone at twice the dose of BDP/BUD, although was unexplained heterogeneity in this effect between trials. There was no difference in the likelihood of oral Candidiasis. Plasma cortisol and 24 hour urinary cortisol were measured frequently but data presentation was limited.. Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing side-effects when given at the same daily dose.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Fluticasone; Humans; Randomized Controlled Trials as Topic

Inhaled fluticasone propionate (FP) is a high potency inhaled corticosteroid used in the treatment of asthma.. 1. To assess the efficacy and safety outcomes in studies that compared inhaled fluticasone at different nominal daily doses in the treatment of chronic asthma. 2. To test for the presence of a dose response effect.. We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997-1999).. Randomised trials in children and adults comparing fluticasone at different nominal daily doses in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data. Quantitative analyses where undertaken using Review Manager 4.0.3 with Metaview 3.1.. 20 studies (>6000 patients) met the inclusion criteria. Methodological quality was high. In non-oral steroid treated asthmatics with mild-moderate disease, a dose response effect was present for morning PEF; when comparing low doses (200 vs 100 mcg/d) Weighted Mean Difference (WMD) 6 L/min, 95% Confidence Interval (CI) 1, 10 L/min; medium-low dose (400-500 vs 100 mcg/d), WMD 8 L/min, 95%CI 1,15 L/min); and high vs low dose (800-1000 vs 50-100 mcg/d), WMD 22 L/min 95% CI 15,29 L/min). There was no dose response in symptoms or rescue beta2 agonist use. Hoarseness and oral Candidiasis was significantly higher with 800-1000 mcg/d than 50-100 mcg/d. In oral steroid dependent disease gain 2000 mcg/d had a greater effect than 1000-1500 mcg/d in likelihood of stopping prednisolone (Peto Odds Ratio 2.8, 95% CI 1.3, 6.3) and reduced daily prednisolone dose (WMD 2.0 mg/d, 95% CI 0.1, 4.0 mg/d).. Effects of fluticasone are dose dependent but relatively small. Patients with mild to moderate disease achieve similar levels of asthma control on low doses of fluticasone (200 mcg/d or less) as they do on high doses (500 mcg/d or greater). In oral corticosteroid dependent asthmatics, reductions in prednisolone requirement may be gained with FP 2000 mcg/d.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Asthma; Chronic Disease; Fluticasone; Humans; Randomized Controlled Trials as Topic

There are limited published data describing the relative efficacy of available treatment options in younger versus older patients with persistent asthma.. To compare the efficacy of fluticasone propionate (FP) and zafirlukast (Z) in younger (12 to 49 years of age) versus older (50 years and older) patients with asthma.. A retrospective analysis of five randomized, double-blind, double-dummy studies 4 to 12 weeks in duration of 1,742 patients <50 years of age and 243 patients aged 50 years or older. Interventions were inhaled fluticasone propionate (FP) 88 microg, oral Z 20 mg, or placebo twice daily.. Treatment with FP resulted in significantly greater improvements than Z in all efficacy measurements (except for nighttime awakenings) regardless of age. In older patients, treatment with FP significantly increased pulmonary function compared with Z: FEV (FP= +0.19 L; placebo = -0.34 L; Z = -0.06 L); AM peak expiratory flow rate [PEFR] (FP = +25 L/minute; placebo = -18 L/minute; Z = +4 L/minute); PM PEFR (FP = +24 L/minute; placebo = -24 L/minute; Z = +5 L/minute; P < or = 0.023; for all comparisons). Compared with Z, treatment with FP in older patients also resulted in significantly greater increases in the percentage of symptom-free days (25% vs 13%) and rescue-free days (35% vs 17%); and significantly greater reductions in albuterol use (-1.6 vs -0.3 puffs/day) and the percentage of patients with exacerbations (2.7% vs 14.3%; P < or = 0.031).. Regardless of age, treatment with FP in patients with asthma significantly improved pulmonary function and overall asthma control. In contrast, treatment with Z in older patients with asthma resulted in small improvements in asthma symptoms, whereas lung function improved minimally or not at all, and exacerbations increased. These data suggest that FP effectively controls inflammation in older patients, whereas Z may mask inflammation and may not provide the level of bronchodilatory or anti-inflammatory activity needed for effective asthma control in older patients.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Tolerance; Female; Fluticasone; Forced Expiratory Volume; Humans; Indoles; Leukotriene Antagonists; Lung; Male; Middle Aged; Peak Expiratory Flow Rate; Phenylcarbamates; Randomized Controlled Trials as Topic; Retrospective Studies; Safety; Sulfonamides; Tosyl Compounds; Treatment Outcome

Oral corticosteroids (CS) are standard treatment for patients discharged from the emergency department (ED) after treatment for acute asthma. Several recent, relatively small trials have investigated the replacement of CS with inhaled corticosteroids (ICS), with varied results and conclusions. This systematic review examined the effect of using ICS in place of CS on outcomes in this setting.. Only randomized controlled trials were eligible for inclusion. Studies in which patients were treated for acute asthma in the ED or its equivalent, and on discharge compared ICS therapy to standard CS therapy, were eligible for inclusion. Trials were identified using the Cochrane Airways Review Group register, searching abstracts and bibliographies, and contacting primary authors and pharmaceutical companies. Data were extracted and methodologic quality assessed independently by two reviewers, and missing data were obtained from authors.. Seven trials, involving a total of 1,204 patients, compared high-dose ICS therapy vs CS therapy after ED discharge. There were no significant differences demonstrated between the treatments for relapse rates (odds ratio, 1.00; 95% confidence interval, 0.66 to 1.52) or in the secondary outcomes of beta-agonist use, symptoms, or adverse events. However, the sample size was not adequate to prove equivalence between the treatments, and severe asthmatics were excluded from these trials.. There is some evidence that high-dose ICS therapy alone may be as effective as CS therapy when used in mild asthmatics on ED discharge; however, there is a significant possibility of a type II error in drawing this conclusion.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Emergencies; Fluticasone; Humans; Patient Discharge; Randomized Controlled Trials as Topic

Several classes of medications are available for the treatment of asthma, and often they must be taken concurrently to achieve asthma control. Based on the understanding of asthma as an inflammatory disease, the National Heart Lung and Blood Institute guidelines provide a stepwise approach to pharmacologic therapy. Corticosteroid therapy, principally inhaled corticosteroid (ICS) therapy, is considered the most effective anti-inflammatory treatment. In cases of moderate-to-severe persistent asthma, the addition of a second long-term control medication to ICS therapy is one recommended treatment option. A combination-product inhaler (Advair, Seretide) was developed to treat both the inflammatory and bronchoconstrictive components of asthma by delivering a dose of the ICS, fluticasone propionate, and a dose of the long-acting beta2-adrenergic (LABA) bronchodilator, salmeterol. The Advair Diskus is available in 3 strengths of fluticasone propionate (100, 250, and 500 microg) and a fixed dose (50 microg) of salmeterol. Combination treatment with both ICS and LABA provides greater asthma control than increasing the ICS dose alone, while at the same time reducing the frequency and perhaps the severity of exacerbations. Furthermore, salmeterol added to ICS therapy provides superior asthma control compared with the addition of leukotriene modifiers or theophylline. The superior control is likely a consequence of the complementary actions of the drugs when taken together, including the activation of the glucocorticoid receptor by salmeterol. By combining anti-inflammatory treatment with a long-acting beta2-agonist in a single inhaler (1 inhalation twice daily), physicians can provide coverage for both the inflammatory and bronchoconstrictive aspects of asthma without introducing any new or unexpected adverse consequences. The most common drug-related adverse events were those known to be attributable to the constituent medications (ICS therapy and/or LABA therapy). Although the benefits of combined ICS plus LABA therapy can be achieved with separate inhalers, the convenience of the combination product may improve patient adherence and may therefore reduce the morbidity of asthma.

Topics: Administration, Inhalation; Adrenergic Agents; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Combinations; Drug Therapy, Combination; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Practice Guidelines as Topic; Salmeterol Xinafoate

The class label warning in the United States for inhaled corticosteroids (ICS's) states that these drugs may reduce growth velocity in children. In this paper, the evidence for this warning is reviewed from a clinical point of view. Children with asthma tend to grow slower than their healthy peers during the prepubertal years because they go into puberty at a later age. However, asthmatic children do achieve a (near) normal adult height. In randomized controlled clinical trials, the use of inhaled beclomethasone, budesonide and fluticasone is associated with a reduced growth during the first months of therapy, in the order of magnitude of approximately 0.5-1.5 cm x yr(-1). It is, however, unlikely that such an effect continues or persists because accumulating evidence shows that asthmatic children, even when they have been treated with ICS for years, attain normal adult height. Individual rare cases have been reported, however, where ICS use was associated with clinically relevant growth suppression. Inhaled corticosteroids are the most effective therapy available for maintenance treatment of childhood asthma. Fear of reduced growth velocity is based on exceptional cases and not on group data. It should, therefore, not be a reason to withhold or withdraw such highly effective treatment in children with asthma.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Biological Availability; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Fluticasone; Glucocorticoids; Growth; Humans

Inhaled corticosteroids are available in the form of a suspension for nebulisation, although the role of this mode of therapy in the treatment of chronic asthma is still unclear.. To assess the efficacy and safety of inhaled corticosteroids delivered via nebuliser versus holding chamber for the treatment of chronic asthma.. We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted the authors of studies and pharmaceutical companies for additional studies and hand-searched the British Journal of Clinical Research, European Journal of Clinical Research and major respiratory society meeting abstracts (1997-1999).. Randomised controlled trials comparing nebuliser to holding chamber in the delivery of inhaled corticosteroids for the treatment of chronic asthma. All age groups of patients were considered. Two reviewers assessed articles for inclusion; two reviewers independently assessed included studies for methodological quality.. One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses were undertaken using Review Manager 4.1 with MetaView 3.1.. Two studies were selected for inclusion (63 subjects), both concerned adults. Methodological quality was variable. Due to design differences it was not appropriate to pool the studies. The single high quality study compared budesonide 2000-8000 mcg delivered via Pari Inhalier Boy jet nebuliser with inspiration-only inhalation to budesonide 1600 mcg via large volume spacer. The nebuliser delivery led to higher morning peak expiratory flow values (25 L/min p<0.01), higher evening values (30L/min, p<0.01), lower rescue beta2 agonist use and symptom scores compared to the holding chamber delivery.. Budesonide in high dose delivered by the particular nebuliser used in the only double-blinded study that could be included in this review was more effective than budesonide 1600 mcg via a large volume spacer. However, it is not clear whether this was an effect of nominal dose delivered or delivery system. Cost, compliance and patient preference are important determinants of clinical effectiveness that have not been assessed. Future studies are needed to evaluate the relative effectiveness of inhaled corticosteroids delivered by different combinations of nebuliser/compressor compared to holding chamber. Moreover, further studies assessing these delivery methods are needed in infants and pre-school children, as these are groups that are likely to be considered for treatment with nebulised corticosteroids.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Drug Delivery Systems; Fluticasone; Glucocorticoids; Humans; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic

Asthma is an inflammatory disease of the airways that is best treated by minimising exposure to factors that provoke the inflammation (e.g. allergens) and by administering drugs that reduce the inflammatory response. The cornerstone of asthma treatment is inhaled corticosteroids. Their effectiveness is a result of their potent and broad anti-inflammatory properties. Antileukotriene drugs (leukotriene modifiers) provide an alternative and novel approach to the treatment of asthma. The novelty of these new compounds is that their effectiveness is firmly based on the pathophysiology of asthma, specifically the role played by the cysteinyl leukotrienes. At the same time, the availability of the antileukotriene drugs has stirred debate over when they should be used and how they compare to inhaled corticosteroids. Although the answers are not fully known at this time, the currently available published and presented data are adequate for us to draw some conclusions about their relative effectiveness and role in asthma treatment. The antileukotriene drugs are more effective than placebo, but they are not as effective as inhaled corticosteroids in improving lung function [measured as the forced expiratory volume in 1 second (FEV(1)) or peak expiratory flow rate (PEFR)], reducing beta(2)-agonist use, and decreasing symptom-free days. In contrast, they may have similar beneficial effects on reducing asthma exacerbations and decreasing peripheral blood eosinophil counts. In the absence of knowing a priori the response of an individual patient to treatment with either therapy, the data favour initiating treatment with an inhaled corticosteroid. However, for patients with mild to moderate disease there are a number of circumstances that support using an antileukotriene drug first. A few examples are aspirin intolerance, predominantly exercise-induced symptoms and problems with using an inhaler or the adverse effects of inhaled corticosteroids such as dysphonia and thrush. For patients with more severe disease, inhaled corticosteroids remain the treatment of choice. Antileukotriene drugs should be considered as add-on therapy, especially in view of their possible complementary effects on reducing airway inflammation.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Clinical Trials as Topic; Female; Fluticasone; Humans; Indoles; Leukotriene Antagonists; Leukotrienes; Male; Peak Expiratory Flow Rate; Phenylcarbamates; Sulfonamides; Tosyl Compounds

To examine the dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma.. Meta-analysis of placebo controlled, randomised clinical trials that presented data on at least one outcome measure of asthma and that used at least two different doses of fluticasone.. Medline, Embase, and GlaxoWellcome's internal clinical study registers.. FEV(1), morning and evening peak expiratory flow, night awakenings, beta agonist use, and major exacerbations.. Eight studies, with 2324 adolescents and adults with asthma, met the inclusion criteria. Data on doses of >500 microg/day were limited. The dose-response curve for the raw data began to reach a plateau at around 100-200 microg/day and peaked by 500 microg/day. A negative exponential model for the data, without meta-analysis, indicated that 80% of the benefit at 1000 microg/day was achieved at doses of 70-170 microg/day and 90% by 100-250 microg/day. A quadratic meta-regression showed that the maximum achievable efficacy was obtained by doses of around 500 microg/day. The odds ratio for patients remaining in a study at a dose of 200 microg/day, compared with higher doses, was 0.73 (95% confidence interval 0.49 to 1.08). Comparison of the standardised difference in FEV(1 )for an inhaled dose of 200 microg/day against higher doses showed a difference in FEV(1) of 0.13 of a standard deviation (-0.02 to 0.29).. In adolescent and adult patients with asthma, most of the therapeutic benefit of inhaled fluticasone is achieved with a total daily dose of 100-250 microg, and the maximum effect is achieved with a dose of around 500 microg/day. However, these findings were limited by the lack of data on individual patients and by the paucity of dose-response studies that included doses of >500 microg/day.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluticasone; Glucocorticoids; Humans; Male; Odds Ratio; Randomized Controlled Trials as Topic

To evaluate the efficacy and safety of changing from low-to-medium doses of other inhaled corticosteroids to low-dose fluticasone propionate.. Data from 11 randomized, double-blind, parallel-group trials in adults (>= 12 years; n = 1453; % predicted FEV1 = 42% to 89%) and 4 trials in children (4-11 years; n = 161; % predicted FEV1 = 50% to 112%) with chronic asthma were retrospectively analyzed. Symptomatic adults (n = 1181) treated with low-to-medium doses of beclomethasone dipropionate (168-672 mcg/day), triamcinolone acetonide (400-1200 mcg/day), or flunisolide (>=1000 mcg/day) were switched to low-dose fluticasone propionate (176 or 200 mcg daily) for 6-26 weeks. Patients (n = 272) remaining on low-dose beclomethasone dipropionate (336 mcg daily) served as controls. Pediatric patients previously treated with low doses of triamcinolone acetonide (4-8 puffs/day), or low-to-medium doses of beclomethasone dipropionate (4-8 puffs/day) or flunisolide (2-6 puffs/day), were changed to low-dose fluticasone propionate (100 mcg daily) for 12-52 weeks.. Improvements in FEV1, morning and evening peak expiratory flow (PEF), rescue albuterol use, asthma symptom scores, and symptom-free days were significantly greater in adults who changed from low-to-medium doses of beclomethasone dipropionate or triamcinolone acetonide to low-dose fluticasone propionate (P <.001). Regardless of the degree of asthma severity, these improvements were 1.5- to 4-fold greater in adult patients changed to low-dose fluticasone propionate vs those remaining on low-dose beclomethasone dipropionate. Significant improvements in lung function, albuterol use, and asthma symptoms (P <=.002) were also seen in pediatric patients who changed from beclomethasone dipropionate, flunisolide, or triamcinolone acetonide to a much lower dose of an inhaled corticosteroid (100 mcg fluticasone propionate daily). Drug-related adverse events were low in adults and children, and were comparable among adults receiving low-dose fluticasone propionate or beclomethasone dipropionate.. Results indicate that patients with persistent asthma can change from other inhaled corticosteroids to a lower dose of fluticasone propionate and still maintain or improve asthma control.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Randomized Controlled Trials as Topic; Triamcinolone Acetonide

The authors describe the scientific rationale for using an inhaled corticosteroid with an inhaled long-acting beta 2-agonist. They discuss the clinical trials demonstrating that using an inhaled corticosteroid with an inhaled long-acting beta 2-agonist provides greater overall asthma control compared with increasing the dose of inhaled corticosteroid. In addition, they review the clinical trials comparing the addition of a leukotriene modifier to an inhaled corticosteroid versus using an inhaled corticosteroid with an inhaled long-acting beta 2-agonist. Discussion also includes descriptions of trials showing reduced exacerbations of asthma when using an inhaled corticosteroid with an inhaled long-acting beta 2-agonist. Finally, the authors provide evidence for the ability to detect deteriorating asthma when using an inhaled corticosteroid with an inhaled long-acting beta 2-agonist, and they provide a comparison of salmeterol and formoterol, two long-acting beta 2-agonists.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchoconstriction; Bronchodilator Agents; Drug Interactions; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Inflammation; Salmeterol Xinafoate

Triamcinolone is a commonly used synthetic corticosteroid that has recently been tested in a large clinical trial for chronic obstructive pulmonary disease and shown to have some benefits. To our knowledge, there are no reviews of the pharmacotherapy of triamcinolone. This review has a brief overview of the pharmacology of triamcinolone, followed by a discussion of the clinical trials with triamcinolone. Triamcinolone is used in the treatment of respiratory inflammation, rheumatoid arthritis and a variety of other inflammatory conditions.

Topics: Administration, Intranasal; Adult; Aerosols; Androstadienes; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Astemizole; Asthma; Child; Clinical Trials as Topic; Conjunctivitis, Allergic; Dose-Response Relationship, Drug; Fluticasone; Humans; Injections, Intramuscular; Loratadine; Lung Diseases, Obstructive; Macular Degeneration; Molecular Structure; Nasal Mucosa; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Structure-Activity Relationship; Triamcinolone

Topics: Administration, Topical; Adrenergic beta-Agonists; Adult; Age Factors; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Drug Interactions; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Meta-Analysis as Topic; Polymorphism, Genetic; Randomized Controlled Trials as Topic; Receptors, Adrenergic, beta-2; Receptors, Glucocorticoid; Respiratory Therapy; Salmeterol Xinafoate; Time Factors

To determine the clinical effectiveness of pressurised metered dose inhalers (with or without spacer) compared with other hand held inhaler devices for the delivery of corticosteroids in stable asthma.. Systematic review of randomised controlled trials.. Cochrane Airways Group trials database (Medline, Embase, Cochrane controlled clinical trials register, and hand searching of 18 relevant journals), pharmaceutical companies, and bibliographies of included trials.. All trials in children or adults with stable asthma that compared a pressurised metered dose inhaler with any other hand held inhaler device delivering the same inhaled corticosteroid.. 24 randomised controlled trials were included. Significant differences were found for forced expiratory volume in one second, morning peak expiratory flow rate, and use of drugs for additional relief with dry powder inhalers. However, either these were within clinically equivalent limits or the differences were not apparent once baseline characteristics had been taken into account. No significant differences were found between pressurised metered dose inhalers and any other hand held inhaler device for the following outcomes: lung function, symptoms, bronchial hyper-reactivity, systemic bioavailability, and use of additional relief bronchodilators.. No evidence was found that alternative inhaler devices (dry powder inhalers, breath actuated pressurised metered dose inhalers, or hydrofluoroalkane pressurised metered dose inhalers) are more effective than the pressurised metered dose inhalers for delivery of inhaled corticosteroids. Pressurised metered dose inhalers remain the most cost effective first line delivery devices.

Topics: Adult; Androstadienes; Asthma; Beclomethasone; Candidiasis, Oral; Child; Fluticasone; Glucocorticoids; Hoarseness; Humans; Hydrocortisone; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Treatment Outcome

Japanese guideline for the diagnosis and management of bronchial asthma was initially reported in 1998 and revised in 2000. This guideline was based on two former guidelines which were made by Japanese Allergology Society in 1993 and NIH.NHLBI in 1995 (GINA). New version of this guideline in 2000 pointed that the efficacy and adverse reaction of leukotriene receptor antagonists, the effectiveness of new inhaled corticosteroid (fluticasone propionate), and transdermal administration of beta-2 stimulant (tulobuterol hydrochloride). The precise evaluation of this guideline in terms of propriety, reliability, applicability and so on was not performed.

Topics: Administration, Cutaneous; Administration, Inhalation; Aminophylline; Androstadienes; Asthma; Evidence-Based Medicine; Fluticasone; Humans; Infusions, Intravenous; Japan; Leukotriene Antagonists; Practice Guidelines as Topic; Program Evaluation; Terbutaline

The pathology of asthma has clarified that the inflammatory process in the pulmonary airways of the asthmatic patients determines asthma symptom activity primarily. Among the anti-inflammatory agents currently available to treat asthma, glucocorticoids are the most effective, and the topically active agents, inhaled corticosteroids (ICS) are the most efficient. In Japan, two ICS are commercially available: beclomethasone dipropionate (BDP) and fluticasone propionate(FP). Both agents have been widely used and their clinical efficacy (BDP vs FP at half the microgram dose of the BDP) are largely comparable. In order to bring asthmatic patients maximal benefits of the ICS, enhancing treatment compliance and giving educations (including how to use the ICS) are mandatory. New ICS, which have better drug delivery and be topically more potent, will be available.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Clinical Trials as Topic; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Patient Education as Topic; Pregnenediones

Several classes of medications are used in the treatment of bronchial asthma. Inhaled corticosteroids are the most potent and effective anti-inflammatory agents. The addition of a long-acting beta 2-adrenergic bronchodilator to inhaled corticosteroids for the treatment of asthma has been shown to improve pulmonary function. Combining an inhaled corticosteroid, fluticasone propionate with a long-acting beta 2-adrenergic bronchodilator, salmeterol in a single inhaler permits treatment of both the inflammatory and bronchoconstrictive components of asthma. Combination treatment with fluticasone and salmeterol improves symptoms and lung function, reduces supplemental use of short-acting beta 2-adrenergic bronchodilator. The combination therapy provides better asthma control and may simplify the management of asthma.

Topics: Administration, Inhalation; Administration, Topical; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Drug Combinations; Fluticasone; Glucocorticoids; Humans; Salmeterol Xinafoate

Inhaled corticosteroid therapy against bronchial asthma has developed rapidly and remarkably during last 10 years. The significance of this therapy has been established in a lot of international guidelines for asthma management. Early intervention, which developed from the concept of step-down therapy, is new therapeutic approach to prevent the remodeling of airway walls deemed as the major cause of irreversible airflow limitation which makes patient chronic and refractory asthmatics. It is comprehensive therapeutic approach which include not only early diagnosis, early intensive corticosteroid therapy, but also environment intervention and enough patient education. In addition to this new therapeutic strategy, we will describe about add-on effect of long-acting beta-2 agonists, theophylline, and leukotriene receptor antagonist.

Topics: Administration, Inhalation; Administration, Topical; Adrenergic beta-Agonists; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Drug Therapy, Combination; Fluticasone; Glucocorticoids; Humans; Leukotriene Antagonists; Practice Guidelines as Topic; Theophylline

Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment of asthma.. 1. To assess efficacy and safety outcomes in studies that compared FP to placebo for treatment of chronic asthma. 2. To explore the presence of a dose-response effect.. We searched the Cochrane Airways Group Trial Register (1999), reference lists of articles, contacted trialists and searched abstracts of major respiratory society meetings (1997-1999).. Randomised trials in children and adults comparing FP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.. One reviewer extracted data. Quantitative analyses where undertaken using Review Manager 4.0.3 with MetaView 3.1.. 28 studies were selected for inclusion (5788 subjects). Methodological quality was high. In non-oral steroid treated asthmatics with mild-moderate disease FP produced improvements from baseline compared to placebo: FEV1 Weighted Mean Difference (WMD) 0.31 litres (95% confidence interval (CI) 0.27 to 0.36 litres); morning PEF WMD 29 /min (95% CI 24 to 33 L/min); symptom scores Standardised Mean Difference (SMD) 0.59 (95% CI 0.47 to 0.71); reduction in rescue beta2 agonist use WMD 1.1 puffs/d (95% CI 0.9 to 1.4). Similar effects were seen for all doses up to 1000 mcg/d. A shallow dose response effect was apparent: eg change in morning PEF with FP 1000 mcg/d WMD 49 L/min (95% CI 41 to 58 L/min). High dose FP reduced the number of patients dependent on prednisolone: FP 1000-1500 mcg/d Peto Odds Ratio 0.07 (95% CI 0.05 to 0.10). FP at all doses led to a greater likelihood of sore throat, hoarseness and oral Candidiasis.. Doses of FP in the range 100-1000 mcg/d are effective. Although there appears to be a dose-response effect, in most patients with mild-moderate asthma improvements with low dose FP are only a little less than those with high doses. High dose FP appears to have worthwhile oral-corticosteroid reducing properties. FP use is accompanied by an increased likelihood of oropharyngeal side effects and this appears to be dose dependent.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Dose-Response Relationship, Drug; Fluticasone; Humans; Randomized Controlled Trials as Topic

To determine whether inhaled steroid therapy causes delayed linear growth in children with asthma.. Medline (1966-1998), Embase (1980-1998), and Cinahl (1982-1998) databases and bibliographies of included studies were searched for randomized, controlled trials of inhaled steroid therapy in children with asthma that evaluated linear growth.. Studies were included if they met the following criteria: subjects 0 to 18 years of age with the clinical diagnosis of asthma; subjects randomized to inhaled beclomethasone, budesonide, flunisolide, fluticasone, or triamcinolone versus a nonsteroidal inhaled control for a minimum of 3 months; single- or double-blind; and outcome convertible to linear growth velocity. English- and non-English-language trials were included.. Data were extracted using a priori guidelines. Methodologic quality was assessed independently by both authors. Outcome was extracted as linear growth velocity.. Included trials were subgrouped by inhaled steroid. The beclomethasone subgroup, with 4 studies and 450 subjects, showed a decrease in linear growth velocity of 1.51 cm/year (95% confidence interval: 1.15,1.87). The fluticasone subgroup, with 1 study and 183 subjects, showed a decrease in linear growth velocity of.43 cm/year (95% confidence interval:.01,.85). Sensitivity analysis in the beclomethasone subgroup, which evaluated study quality, mode of medication delivery, control medication, and statistical model, showed similar results.. This meta-analysis suggests that moderate doses of beclomethasone and fluticasone in children with mild to moderate asthma cause a decrease in linear growth velocity of 1.51 cm/year and.43 cm/year, respectively. The effects of inhaled steroids when given for >54 weeks, or on final adult height, remain unknown.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Body Height; Budesonide; Child; Child, Preschool; Fluocinolone Acetonide; Fluticasone; Growth; Humans; Infant; Infant, Newborn; Steroids; Triamcinolone

Topics: Administration, Topical; Aerosol Propellants; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chemistry, Pharmaceutical; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated

The long-acting beta2-agonist salmeterol and the corticosteroid fluticasone propionate are available as a combination inhalation device for the treatment of persistent asthma. Well designed studies in adults, adolescents and children aged > or =4 years, demonstrate that combined salmetero/fluticasone propionate 50/100, 50/250 and 50/500 microg administered via a dry powder inhaler (DPI) is clinically equivalent to concurrent delivery of the same dosages of the 2 drugs via separate DPIs. In adults and adolescents, combined salmeterol/fluticasone 50/100 and 50/250 microg twice daily produced rapid improvements in lung function that were consistently greater than those in patients receiving monotherapy twice daily salmeterol 50 microg, fluticasone propionate 100 or 250 microg or placebo in 2 well designed studies. Recipients of the combination had a significantly greater probability of completing 12 weeks of treatment than patients receiving monotherapy or placebo. The combination also produced significant improvements between baseline and end-point in all secondary outcome variables (morning and evening peak expiratory flow, daytime symptom scores, days and nights without asthma symptoms and requirements for as-needed beta-agonists) and health-related quality of life (QOL). Combination therapy was superior to monotherapy with salmeterol and placebo for all outcomes in both studies, and was superior to fluticasone propionate 100 microg for all but 1 outcome (nights without awakenings) in 1 study. Similar results were obtained in patients who had previously been using short acting beta2-agonists alone. Combined twice daily salmeterolfluticasone propionate 50/100 and 50/250 microg produced greater improvements in lung function than inhaled budesonide at higher dosages than fluticasone propionate in the combination. Combined salmeterol/fluticasone propionate 50/250 microg produced similar improvements in lung function to concurrent budesonide 800 microg plus formoterol 12 microg when given twice daily for 12 weeks. In another 12-week trial, combined salmeterol/fluticasone propionate 50/100 microg was more effective than oral montelukast 10 mg/day plus fluticasone propionate 100 microg twice daily in patients with suboptimally controlled asthma. Salmeterol/fluticasone is more cost effective than monotherapy with fluticasone propionate or budesonide. The most frequent adverse events associated with salmeterol/fluticasone propionate are headache, throat irritation. Combined salmeterol/fluticasone propionate is as effective as the 2 drugs given concurrently via separate inhalers and significantly more effective than either drug given alone at the same nominal dosage. The combination is also significantly more effective than montelukast plus fluticasone propionate or monotherapy with inhaled budesonide. Furthermore, the combination is more cost effective than inhaled corticosteroid monotherapy.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Costs; Drug Resistance; Drug Therapy, Combination; Economics, Pharmaceutical; Female; Fluticasone; Humans; Infant; Infant, Newborn; Male; Middle Aged; Salmeterol Xinafoate

Contemporary asthma management guidelines list inhaled corticosteroids as the preferred controller medication for patients with persistent asthma. Despite the availability of explicit guidelines, there is evidence that these agents are underused and that guidelines are not always adhered to. Fluticasone propionate is one of several inhaled corticosteroids used for the treatment of asthma. Like other agents of its class, its efficacy is backed by extensive clinical data. More recently, the quality of life of recipients of fluticasone propionate and its relative cost effectiveness have been investigated. A series of comparative analyses show that inhaled fluticasone propionate is more cost effective than oral zafirlukast and triamcinolone acetonide and slightly more cost effective than flunisolide in adult patients with asthma. Analyses used cost per symptom-free day and/or cost per successfully treated patient as outcome measures and were generally conducted from the perspective of the third-party payer. When administered at a microgram dose of half or less than budesonide (as is therapeutically appropriate), the cost effectiveness of fluticasone propionate was similar to or better than that of budesonide. In children, fluticasone propionate was more cost effective per treatment success compared with inhaled sodium cromoglycate. Quality-of-life assessments in patients with mild to moderate disease show that inhaled fluticasone propionate achieved improvements which were deemed to be clinically meaningful in patients with mild to moderate asthma; these changes were significantly greater than those achieved with oral zafirlukast, inhaled triamcinolone acetonide or placebo. Greater improvements were evident with inhaled fluticasone propionate in patients with severe disease.. In addition to the considerable body of clinical evidence supporting the use of inhaled fluticasone propionate in patients with asthma, accumulating short term cost-effectiveness data also suggest that this agent can be administered for a similar or lower cost per outcome than other inhaled corticosteroids or oral zafirlukast. Importantly, the clinical benefits offered by fluticasone propionate in patients with persistent asthma are accompanied by clinically significant improvements in quality of life.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Cost-Benefit Analysis; Economics, Pharmaceutical; Fluticasone; Humans

The results of a recent meta-analysis comparing 2 inhaled corticosteroids, fluticasone propionate (FP) and budesonide, demonstrated that FP had an improved efficacy-to-safety ratio compared with budesonide. However, limited data are available on the relative economic benefits of these 2 regimens.. This pharmacoeconomic analysis used individual patient data from studies in the meta-analysis to compare the relative cost-efficacy of 2 asthma regimens from the perspective of a US third-party payer.. This analysis included all 7 studies in the meta-analysis that compared budesonide with FP dosed at approximately half the dose of budesonide and that included measurement of daily morning peak expiratory flow (PEF).. The total daily per-person cost of asthma management was higher for patients treated with budesonide than with FP ($3.00 vs $2.25, respectively). Treatment with FP had greater cost-efficacy than treatment with budesonide, based on a range of outcome measures that included improvement in morning PEF, symptom-free days, and episode-free days. The daily cost per effectively treated patient (an increase in PEF of > or = 10%) was $5.62 with FP and $10.05 with budesonide. The cost per symptom-free day was $4.36 with FP, compared with $6.67 with budesonide. The cost per episode-free day was $5.60 with FP and $9.42 with budesonide. The pharmacoeconomic difference continued to favor FP as the criteria for success were made more stringent and the cost of budesonide was lowered.. Based on data from the 7 randomized, controlled trials, treatment of asthma with FP was more effective and less expensive, using US health care assumptions and costs, than treatment with budesonide.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Cost-Benefit Analysis; Fluticasone; Humans

Cost estimates from developed countries indicate that asthma accounts for up to 2% of the economic cost of all diseases. A large proportion of asthma-related costs are attributable to poor asthma control. Treatment strategies which improve clinical outcomes in patients with asthma, therefore, have the potential for significant economic benefits, and it is important to evaluate new asthma therapies for cost effectiveness. Several studies have established that salmeterol and fluticasone propionate combined in a single dry powder inhalation device are at least as effective as a combination of the 2 drugs administered via separate dry powder inhalers and more effective than monotherapy with fluticasone propionate or budesonide. Importantly, pharmacoeconomic analysis of several of these studies show that the salmeterol/fluticasone propionate combination is cost effective relative to monotherapy with fluticasone propionate or budesonide. Although the total cost of asthma management tended to be slightly higher with salmeterol/fluticasone propionate than with inhaled corticosteroid monotherapy, in most cases mean cost-effectiveness ratios were lower (i.e. more favourable) for salmeterol/fluticasone propionate than either fluticasone propionate or budesonide. Cost effectiveness was assessed according to 3 end-points: successfully treated weeks, symptom-free days and episode-free days. Mean cost-effectiveness ratios consistently favoured salmeterol/fluticasone propionate over the comparator drug for the end-point successfully treated weeks, and in most cases the other 2 end-points also favoured the combination product over the comparator. In a further study, salmeterol/fluticasone was also less costly than therapy with formoterol and budesonide administered via 2 separate inhalers. Studies of health-related quality of life (HR-QOL) using the Asthma Quality of Life Questionnaire indicate that salmeterol/fluticasone propionate produces clinically meaningful improvements in overall HR-QOL relative to salmeterol monotherapy or placebo. Improvements in overall HR-QOL were statistically significantly greater for salmeterol/fluticasone propionate than with fluticasone propionate or budesonide alone, although the differences between treatments did not exceed the threshold for clinical significance. In conclusion, short term cost-effectiveness data show that salmeterol/fluticasone propionate is more cost effective than the inhaled corticosteroids budesonide and fluticasone

Topics: Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Drug Combinations; Fluticasone; Humans; Salmeterol Xinafoate

Fluticasone propionate (FP) is a potent inhaled corticosteroid (ICS) for the treatment of asthma. It is currently marketed in both the United States (as Flovent) and Europe (as Flixotide). Fluticasone is available in both aerosolised metered dose inhaler (MDI) and dry powder devices, with dosages ranging from 44-500 micrograms/puff. FP has been extensively studied in both children and adults; efficacy has been documented across the entire spectrum of asthma severity, including corticosteroid-dependent disease. Clinical data with FP strongly corroborates the in vitro pharmacokinetic and pharmacodynamic studies that FP is at least twice as potent as beclomethasone dipropionate (BDP), budesonide (BUD) or triamcinolone acetonide (TAA). Both objective (lung function) and subjective (symptoms, beta-agonist use and quality of life) outcomes are improved with FP treatment. Extensive post-marketing surveillance with FP suggests that it is more cost-effective than BUD and flunisolide (FLU) when analysed by an overall healthcare cost perspective. Most of the benefits arise from decreased hospitalizations, emergency room visits and physician-office visits. Extensive safety data with FP documents no clinically meaningful effects on bone mass, nor impairment of growth velocity in children. Considering the efficacy and safety data along with the ability to optimise patient's asthma therapy using the delivery devices and strengths available, FP has become a leader in the ICS marketplace to date.

Topics: Administration, Inhalation; Androstadienes; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Clinical Trials as Topic; Fluticasone; Humans

The past decade has seen significant advances in the available treatments for asthma. These include longer-acting bronchodilating agents, high topical potency inhaled corticosteroids, and agents that interfere with leukotriene production or action. Table 3 summarizes the clinical effects of the newer therapeutic agents reviewed. Experimental therapies for the steroid-dependent patient have also been discussed. Although clinical trials to date have established many of these as effective in asthma, the results of ongoing, large, multicenter studies investigating the relative merits of these therapies, alone and in combination, will further clarify how to maximize the utility of these agents in the treatment of asthma.

Topics: Administration, Inhalation; Administration, Topical; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Clinical Trials as Topic; Drug Combinations; Fluticasone; Glucocorticoids; Humans; Leukotriene Antagonists; Multicenter Studies as Topic; Salmeterol Xinafoate

The past decade has seen significant advances in the available treatments for asthma. These include longer-acting bronchodilating agents, high topical potency inhaled corticosteroids, and agents that interfere with leukotriene production or action. Table 3 summarizes the clinical effects of the newer therapeutic agents reviewed. Experimental therapies for the steroid-dependent patient have also been discussed. Although clinical trials to date have established many of these as effective in asthma, the results of ongoing, large, multicenter studies investigating the relative merits of these therapies, alone and in combination, will further clarify how to maximize the utility of these agents in the treatment of asthma.

Topics: Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Cyclosporine; Fluticasone; Forced Expiratory Volume; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Indoles; Leukotriene Antagonists; Lidocaine; Methotrexate; Phenylcarbamates; Salmeterol Xinafoate; Sulfonamides; Tosyl Compounds; Treatment Outcome

To appraise the data on systemic adverse effects of inhaled corticosteroids.. A computerized database search from January 1, 1966, through July 31, 1998, using MEDLINE, EMBASE, and BIDS and using appropriate indexed terms. Reports dealing with the systemic effects of inhaled corticosteroids on adrenal gland, growth, bone, skin, and eye, and reports on pharmacology and pharmacokinetics were reviewed where appropriate. Studies were included that contained evaluable data on systemic effects in healthy volunteers as well as in asthmatic children and adults. A statistical meta-analysis using regression was performed for parameters of adrenal suppression in 27 studies.. Marked adrenal suppression occurs with high doses of inhaled corticosteroid above 1.5 mg/d (0.75 mg/d for fluticasone propionate), although there is a considerable degree of interindividual susceptibility. Meta-analysis showed significantly greater potency for dose-related adrenal suppression with fluticasone compared with beclomethasone dipropionate, budesonide, or triamcinolone acetonide, whereas prednisolone and fluticasone propionate were approximately equivalent on a 10:1-mg basis. Inhaled corticosteroids in doses above 1.5 mg/d (0.75 mg/d for fluticasone propionate) may be associated with a significant reduction in bone density, although the risk for osteoporosis may be obviated by post-menopausal estrogen replacement therapy. Although medium-term growth studies showed suppressive effects with 400-microg/d beclomethasone dipropionate, there was no evidence to support any significant effects on final adult height. Long-term, high-dose inhaled corticosteroid exposure increases the risk for posterior subcapsular cataracts, and, to a much lesser degree, the risk for ocular hypertension and glaucoma. Skin bruising is most likely to occur with high-dose exposure, which correlates with the degree of adrenal suppression.. All inhaled corticosteroids exhibit dose-related systemic adverse effects, although these are less than with a comparable dose of oral corticosteroids. Metaanalysis shows that fluticasone propionate exhibits greater dose-related systemic bioactivity compared with other available inhaled corticosteroids, particularly at doses above 0.8 mg/d. The long-term systemic burden will be minimized by always trying to achieve the lowest possible maintenance dose that is associated with optimal asthmatic control and quality of life.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bone and Bones; Budesonide; Dose-Response Relationship, Drug; Eye; Fluticasone; Glucocorticoids; Growth; Humans; Prednisolone; Skin; Triamcinolone

Fluticasone propionate is a corticosteroid with comparatively high receptor affinity and topical activity. Inhaled fluticasone propionate < or =500 microg/day provided effective corticosteroid maintenance treatment in patients with mild to moderate asthma in randomised, controlled clinical studies of 4 to 24 weeks in duration. Dosages of 50 to 250 microg twice daily produced consistent improvement in spirometric measures of lung function, reduced the frequency of as-needed beta2-agonist bronchodilator use, asthma symptom scores and night-time wakenings, and prevented asthma exacerbations compared with placebo. Fluticasone propionate < or =250 microg twice daily provided significantly greater improvements in lung function than nedocromil 4 mg 4 times daily, theophylline (5 to 15 mg/L) or zafirlukast 20 mg twice daily. Health-related quality of life improved significantly with fluticasone propionate 88 microg twice daily, but not zafirlukast 20 mg twice daily or placebo. In comparative trials in which fluticasone propionate was given at half the dosage of beclomethasone dipropionate, budesonide or flunisolide, fluticasone propionate < or =250 microg twice daily produced equivalent or greater improvement in spirometric parameters and equivalent reductions in the use of as-needed beta2-agonists than beclomethasone dipropionate, budesonide or flunisolide. Fluticasone propionate 250 microg twice daily was generally more effective than triamcinolone acetonide 200 microg 4 times daily in two 24-week trials. The combination of inhaled fluticasone propionate < or =250 plus salmeterol < or =50 microg twice daily allowed for the use of lower dosages of the inhaled corticosteroid. The incidence of adverse events in patients receiving inhaled fluticasone propionate 50 to 250 microg twice daily was similar to that in beclomethasone dipropionate 168 to 500 microg twice daily and budesonide 100 to 600 microg twice daily recipients and greater than that in recipients of triamcinolone acetonide 200 microg 4 times daily in comparative trials. The incidence of oral candidiasis was < or =8% in patients treated with fluticasone propionate < or =250 microg twice daily or other agents. There was no evidence of clinically significant hypothalamo-pituitary-adrenal (HPA) axis suppression with fluticasone propionate < or =250 microg twice daily in comparative trials.. Inhaled fluticasone propionate < or =500 microg/day is an effective antiinflammatory therapy for mild to moderate asthma in adolescents and adults. The drug is more effective than nedocromil, theophylline or zafirlukast and is at least as effective as other inhaled corticosteroids administered at twice the fluticasone propionate dosage. The addition of inhaled salmeterol allows the use of lower maintenance dosages of fluticasone propionate. The drug is well tolerated and there is no evidence of a clinically significant effect of this dosage on HPA axis function. Hence, fluticasone propionate < or =500 microg/day is a particularly suitable agent for patients with mild to moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Clinical Trials as Topic; Drug Therapy, Combination; Fluticasone; Humans

Current evidence suggests that addition of the long-acting beta2-agonist salmeterol to an inhaled corticosteroid in patients with persistent asthma symptoms provides greater clinical benefit than doubling the dosage of the inhaled corticosteroid. Fixed combination salmeterol/fluticasone propionate in 3 different fluticasone propionate dosage strengths administered via the Diskus powder inhaler does not result in any untoward interaction that affects the pharmacodynamic or pharmacokinetic profiles of the individual drugs, or their adverse effect profiles - including the influence of the corticosteroid on plasma cortisol levels. Administration of fixed combination salmeterol/ fluticasone propionate to both adults and children with persistent asthma provides greater improvements in lung function than either agent alone, and at least equal effectiveness to the same dosages of the 2 agents given by separate powder inhalers. Preliminary reports indicate that combination therapy has also demonstrated superior efficacy to budesonide (fluticasone propionate dosages were 25% those of budesonide). The most commonly encountered adverse effects in clinical trials with combined salmeterol/fluticasone propionate therapy have been oropharyngeal candidiasis. hoarseness/dysphonia, throat irritation, headache, tachycardia/palpitations, tremor and dizziness (all in < or =5% of patients).

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Clinical Trials as Topic; Drug Combinations; Fluticasone; Humans; Hydrocortisone; Nebulizers and Vaporizers; Salmeterol Xinafoate

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Combinations; Fluticasone; Humans; Salmeterol Xinafoate

Asthma is a chronic inflammatory disorder of the airways characterized by variable airflow limitation and airway hyperresponsiveness. The type of inflammatory response in asthma is compatible with a major contribution of professional antigen-presenting cells. The airways in chronic obstructive pulmonary disease (COPD) are also markedly inflamed; however, the predominant types of inflammatory cells and the main anatomical site of the lesion appear to differ from those in asthma. COPD is characterized by reduced maximum expiratory flow and slow forced emptying of the lungs. Steroids are the most prominent medication used in the treatment of asthma and COPD; however, the beneficial effect of steroid treatment in COPD is subject of debate. We investigated the efficacy of fluticasone propionate (FP) treatment in atopic asthmatics and in COPD patients with bronchial hyperreactivity who smoke. The effect of the treatment on bronchial hyperreactivity and indices of the methacholine dose-response curve were analysed, as well as indices of inflammation of the airway mucosa with special emphasis on the antigen presenting dendritic cell. Treatment of allergic asthmatic patients resulted in improvement of lung function (FEV1), a decrease in bronchial hyperresponsiveness and a decrease of maximal airway narrowing. During the FP-treatment of COPD patients, FEV1 remained stable, while FEV1 deteriorated significantly in the placebo group. Therefore, steroid treatment may have a beneficial effect in COPD patients with bronchial hyperresponsiveness (BHR). Since immunohistochemical analysis of bronchial biopsy specimens from asthma and COPD patients show disease-specific aspects of inflammation, the anti-inflammatory effect of FP is obtained through modulation of different cell populations in asthma and COPD.

Topics: Androstadienes; Animals; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Dendritic Cells; Dose-Response Relationship, Drug; Fluticasone; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Methacholine Chloride

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Biomarkers; Budesonide; Fluticasone; Humans; Hydrocortisone

Topics: Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Drug Combinations; Fluticasone; Humans; Salmeterol Xinafoate

To present value of cost effectiveness evaluation in asthma treatment Material and methods. Meta-analysis of asthma treatment studies compared with data from National Healthcare Plan in Slovenia.. Patients treated with fluticasone propionate (FP) were successfully controlled for 41.7% of treated weeks compared with 34.1% in the group treated with budesonide (B) (p < 0.001). Purchase price for FP (1.524 SIT/week) is not significantly different from B (1.462 SIT/week). The overall mean weekly cost per patient was 3.077 SIT for patient treated with B and 1.916 SIT for patient treated with FP. Cost of health care contacts were 56 SIT in the FP group and 1.275 SIT in B group per week. The total expenditure per week of successful treatment would be 4.594 SIT/week in the FP group and 9.025 SIT/week in patients treated with B.. It is evident that by evaluation of purchase price only no final conclusion of cost effectiveness of treatment of asthma is possible.. Limited resources in the health care could be properly distributed only after carefully weighting costs and comparing outcomes.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Cost-Benefit Analysis; Fluticasone; Humans; Slovenia

During therapy with inhaled corticosteroids (ICS) of asthmatic children studies examining growth over several weeks using a knemometer showed a dose-dependent reduction of lower leg growth. During maintenance treatment with beclomethasone 400 micrograms/day for several months the growth of asthmatic children was reduced by approximately 1 cm/year compared with contemporaries who had not been treated with this substance. No such growth retardation was found in studies on long-term therapy with budesonide (400-800 micrograms/day) or fluticasone (100-200 micrograms/day). However, differences between ICS are difficult to establish or to exclude, since the systemic availability may vary, due for instance to the properties of the inhaler and the individual inhaling technique. It appears that most children with asthma treated with ICS perform a catch-up growth so that they reach a normal height as young adults. Since growth retardation if any mostly occurs during the first three months of the treatment, growth of asthmatic children must be monitored carefully. When growth is reduced by > 0.25 standard deviation score within 1 year, the use of ICS needs to be reconsidered. This decision can best be made by a paediatrician or after consulting one.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Body Height; Budesonide; Child; Child Development; Child, Preschool; Dose-Response Relationship, Drug; Fluticasone; Humans

Topics: Adolescent; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Cost-Benefit Analysis; Double-Blind Method; Drug Combinations; Female; Fluticasone; Humans; Male; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

The relative clinical efficacy and systemic effects of different inhaled corticosteroids is controversial. To obtain further information on this matter, the authors have performed meta-analysis of seven trials comparing fluticasone propionate (FP) with budesonide (Bud), and seven trials comparing FP with beclomethasone dipropionate (BDP) for the treatment of asthma of all severities in adult and paediatric patients. In all cases, the drugs were compared at clinically equivalent doses, i.e. FP was given at half (or less) the microgram dose. The total number of patients was 1980 (1000 treated with FP 200-800 micrograms day-1 and 980 with Bud 400-1600 micrograms day-1), and 1584 patients in the second analysis (780 treated with FP 200-1000 micrograms day-1 and 804 with BDP 400-2000 micrograms day-1). FP significantly improved mean morning peak expiratory flow rate (PEFR) compared with Bud, with an overall difference of +11 l min-1. Analysis of serum cortisols showed no differences between FP and Bud treatment at low doses, but at higher dosages, and overall, significant differences in favour of FP were observed. In the second meta-analysis, no significant differences in PEFR were observed between FP and BDP in any of the seven individual studies or in the pooled analysis. Analysis of serum cortisols showed a similar trend to the previous analysis, however, no overall difference in serum cortisol results were seen between FP and BDP. In conclusion, the pooled analysis shows that FP at half the dose (or less) is more effective than Bud and as effective as BDP in improving PEFR; in addition, these improvements were achieved with a reduction in cortisol suppression compared with BUD and with no greater degree of cortisol suppression compared with BDP. This demonstrates, in patients with asthma, that FP has an improved efficacy to safety ratio compared with older inhaled corticosteroids.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Child; Drug Administration Schedule; Fluticasone; Humans; Hydrocortisone; Peak Expiratory Flow Rate

Fluticasone propionate (FP) is a trifluorinated glucocorticoid based on the androstane nucleus. It was selected for development from structure-activity relationships (topical anti-inflammatory, cutaneous vasoconstriction, and hypothalamic-pituitary-adrenal axis suppression) of a series of 17beta-carbothioates. FP is 3-, 300-, and 1000-fold more lipophilic than beclomethasone dipropionate, budesonide, and triamcinolone acetonide, respectively. FP has an absolute affinity (KD) for the glucocorticoid receptor of 0.5 nmol/L and a relative receptor affinity 1.5-fold higher than beclomethasone-17-monopropionate (17-BMP) and mometasone furoate, 3-fold higher than budesonide, and 20-fold higher than flunisolide and triamcinolone acetonide. The rate of association of FP with the receptor is faster and the rate of dissociation slower than other corticosteroids. The resulting half-life of the FP active steroid-receptor complex is >10 hours, compared with approximately 5, 7.5, and 4 hours for budesonide, 17-BMP, and triamcinolone acetonide, respectively. FP has high selectivity for the glucocorticoid receptor, with little or no activity at other steroid receptors. FP is more potent than beclomethasone dipropionate, budesonide, triamcinolone acetonide, and mometasone furoate in inhibiting human T-cell migration and proliferation, inhibiting CD4+ T-cell cytokine and basophil histamine release, attenuating adhesion molecule expression, stimulating inflammatory cell apoptosis, and inducing cellular antiprotease release. In asthma patients, FP decreases the number of CD3+, CD4+, CD8+, and CD25+ T cells, mast cells, and eosinophils in bronchial biopsies, in addition to suppressing CD1a-dendritic and IgE+ cells and HLA-DR. FP, therefore, has a good pharmacologic profile for a topical steroid with increased intrinsic glucocorticoid potency and potent anti-inflammatory activity.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Fluticasone; Humans; Lung; Receptors, Glucocorticoid; Solubility; Structure-Activity Relationship

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Drug Evaluation; Fluticasone; Humans; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Fluticasone propionate (FP) is a new topical corticosteroid spray for the treatment of allergic rhinitis and asthma. FP has been shown to be effective for the treatment of adult and pediatric asthma, even at rather low doses (25 microg twice daily [b.i.d.]); many studies in asthma have shown clinical efficacy of fluticasone at half the dose of the comparison steroid (such as beclomethasone dipropionate [BDP] or budesonide [BUD]). However, exact dose comparisons cannot be made because dose-ranging comparison studies have not been done. Studies in allergic rhinitis in children and adults have shown good efficacy in FP-treated patients at a dose of 200 microg once daily (o.d.), intranasally. In summary, FP is effective in both asthma and allergic rhinitis.. FP has minimal systemic activity because the portion of drug that is swallowed is not absorbed from the gut. Thus, the amount available for systemic activity is only that which is absorbed through the nasal mucosa (in the treatment of rhinitis) or through the alveoli of the lungs (in the treatment of asthma). When laboratory assays of adrenal function or bone formation are measured, FP and other inhaled corticosteroids can be shown to cause suppression of these markers, especially at high doses. There have been no consistent reports of clinical adrenal suppression or osteoporosis caused by FP. In summary, the risk-benefit ratio of FP at the usual doses (therapeutic ratio) is very favorable. High doses may show evidence of suppression of the hypothalamic pituitary axis as measured by in vitro tests, but evidence of corresponding clinical adverse effects is lacking.

Topics: Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Fluticasone; Humans; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Risk Assessment

The early inflammatory response during allergic rhinitis and asthma is associated with IgE-mediated mast cell activation and resultant release of primary inflammatory mediators. The late phase reaction is characterized by recruitment, activation and tissue infiltration of leucocyte populations, including T lymphocytes, eosinophils, basophils and neutrophils. T helper type 2 CD4+ cells, a T lymphocyte subset with a distinctive cytokine profile, are thought to regulate the recruitment and activation of other effector cells. This review discusses the results of studies conducted under experimental and natural conditions of allergen exposure, which confirm the presence of eosinophilia, changes in lymphocyte populations, and increased expression of a TH2-cytokine profile in the nasal mucosa following allergen-induced rhinitis, and the alleviation of both clinical symptoms and inflammatory responses by prior treatment with topical fluticasone propionate. Similar effects are demonstrated to occur in the lower airway following allergen challenge in asthma patients, and to be ameliorated by oral corticosteroid therapy. These studies add weight to the argument that asthma and rhinitis share a common pathophysiology characterized by similar inflammatory events, and should both benefit from early preventative treatment with topical corticosteroids.

Topics: Administration, Topical; Adrenal Cortex Hormones; Androstadienes; Anti-Inflammatory Agents; Asthma; Fluticasone; Glucocorticoids; Humans; Interferon-gamma; Interleukin-4; Interleukin-5; Leukocytes; Lung; Nasal Mucosa; Rhinitis

This report reviews the evidence for the role of fluticasone propionate in the management of asthma, based on efficacy and safety trial data in over 4000 adults and more than 1600 children suffering from asthma of varying severity. Overall, fluticasone propionate at half the daily dose is at least as effective as budesonide and as effective as beclomethasone dipropionate across a range of doses.

Topics: Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Biomarkers; Child; Child, Preschool; Clinical Trials as Topic; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Female; Fluticasone; Growth; Humans; Male

Topics: Administration, Inhalation; Administration, Topical; Adrenal Glands; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Dose-Response Relationship, Drug; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Growth; Humans; Osteoporosis; Pregnenediones; Triamcinolone Acetonide

Topics: Absorption; Administration, Topical; Adolescent; Adult; Aerosols; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Child; Drug Administration Schedule; Fluticasone; Glucocorticoids; Humans; Infant; Practice Guidelines as Topic; Pregnenediones; Risk Factors

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Dose-Response Relationship, Drug; Fluticasone; Humans; Pregnenediones; Risk Assessment

Bronchial asthma is characteristic of chronic airway inflammatory disorder which many inflammatory cells play a role, BDP therefore has become a basic drug (controller) in the treatment of asthma. Recently new dry powder inhalation systems of corticosteroid such as fluticasone propionate (Diskhaler) and budesonide (Turbuhaler) have been studied to examine the dose response clinical efficacy to BDP. Clinical efficacy of both drugs are equivocal to double dose of BDP. These excellent drugs will be soon available for clinical use in Japan.

Topics: Administration, Oral; Androstadienes; Anti-Inflammatory Agents; Asthma; Budesonide; Clinical Trials as Topic; Dose-Response Relationship, Drug; Fluticasone; Humans; Japan; Nebulizers and Vaporizers; Powders; Pregnenediones

Fluticasone propionate (FP) is a novel androstane glucocorticoid with potent anti-inflammatory activity which has been effectively used, intranasally, as therapy for seasonal and allergic perennial rhinitis. When taken by the inhaled route, FP has shown significant therapeutic efficacy in the management of asthma. Fluticasone propionate is a highly lipophilic molecule with good uptake, binding and retention characteristics in human lung tissue. Fluticasone propionate has high glucocorticoid receptor selectivity and affinity, demonstrating rapid receptor association and slow receptor dissociation. In vitro, FP has been shown to potently inhibit T lymphocyte proliferation, cytokine generation, tumour necrosis factor alpha (TNF-alpha)-induced adhesion molecule expression, interleukin-5-induced eosinophilia, mucosal oedema and toluene 2,4-diisocyanate-induced mast cell proliferation, while promoting secretory leucocyte protease inhibitor production and eosinophil apoptosis. In human studies, FP has demonstrated marked vasoconstrictor potency in normal subjects and inhibited antigen-induced mucosal platelet activating factor/eicosanoid production, T lymphocytes and CD25+ cells in patients with rhinitis. Biopsy data from mild asthmatics demonstrate FP-associated reduction in CD3, CD4, CD8 and CD25 cells, with an accompanying reduction in eosinophil and mast cell markers. Clinical studies have evaluated lung function, bronchial reactivity, exacerbation rates and oral corticosteroid-sparing effect. Results show that FP has at least twice the clinical potency of beclomethasone dipropionate and budesonide. This appears to be achieved without an accompanying increase in systemic effects, suggesting a therapeutic index which may be higher than other currently available inhaled corticosteroids.

Topics: Androstadienes; Animals; Anti-Inflammatory Agents; Asthma; Clinical Trials as Topic; Dose-Response Relationship, Drug; Fluticasone; Humans; Lung; Rhinitis

Fluticasone propionate is an androstane carbothioate glucocorticosteroid with almost twice the topical anti-inflammatory potency of beclomethasone dipropionate. Importantly, it is not appreciably absorbed from the gastrointestinal tract. However, the fraction of active drug absorbed from the lungs after inhalation, and therefore total systemic availability, has yet to be determined. Inhaled fluticasone propionate administered at dosages of 1500 micrograms/day for 1 year or 2000 micrograms/day for 6 weeks did not cause clinically significant pituitary-adrenal suppression. Preliminary data from 2 published trials also indicate no significant effect on growth in children. However, wider clinical experience is needed to clarify the effects of long term administration on pituitary-adrenal function, bone metabolism and attainment of adult height in children. In clinical studies, inhaled fluticasone propionate was at least as effective as beclomethasone dipropionate or budesonide when administered at half the dosage of the comparators in patients with mild to moderate or severe asthma. Limited data suggest that fluticasone propionate also has considerable potential in the management of childhood asthma. In trials of up to 1 year in duration, fluticasone propionate appeared to be well tolerated by both adults and children. Whether an improved tolerability profile compared with other corticosteroids is a major clinical benefit of the extremely low oral bioavailability of inhaled fluticasone propionate requires confirmation. Nevertheless, on the basis of available data from initial clinical trials of mostly limited duration, inhaled fluticasone propionate offers an effective treatment option for the management of asthma, with the potential of an enhanced safety profile.

Topics: Administration, Inhalation; Adrenal Glands; Androstadienes; Anti-Inflammatory Agents; Asthma; Bone and Bones; Child; Child, Preschool; Clinical Trials as Topic; Dose-Response Relationship, Drug; Fluticasone; Humans

Inhaled corticosteroids have an essential role in the management of many patients with asthma, improving control and reducing the need for oral corticosteroids. Used in conventional dosage inhaled corticosteroids are very safe; in high dosage systemic effects are more evident. Fluticasone propionate (Flixotide--Allen & Hanburys), a new inhalation corticosteroid, is promoted as being more potent than conventional preparations (beclomethasone dipropionate and budesonide) and less likely to cause systemic effects. Is this claim justified and what is the place of fluticasone propionate in asthma prophylaxis?

Topics: Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Asthma; Drug Costs; Fluticasone; Glucocorticoids; Humans

Glucocorticoids are frequently required for management of cough because of inflammatory airway disease (IAD) and airway collapse (AWC).. To determine the efficacy and feasibility of inhaled administration of corticosteroids in controlling cough in dogs with noninfectious airway disease.. Thirty-six client-owned dogs.. Dogs were prospectively recruited for this placebo-controlled cross-over study. Inflammatory airway disease was diagnosed through bronchoalveolar lavage cytology. Airway collapse was diagnosed through bronchoscopy, or if dogs were unsuitable anesthetic candidates, by crackles on auscultation, radiographic changes in airway diameter, or fluoroscopy. Dogs were randomly assigned to receive placebo or fluticasone propionate for the first 2 weeks of the trial then crossed over to fluticasone. A quality of life (QOL) survey (best score 0, worst score 85) was completed at 0 and 6 weeks. A visual-analog cough survey was submitted at 0, 2, 4, and 6 weeks to assess cough, feasibility, and adverse effects of treatment.. For 32 dogs, QOL score at study end (mean 11.3 ± 9.7) was significantly lower (P < .0001) compared to entry (mean 28.1 ± 14.1), with a median change of 69% in QOL score, indicating improved quality of life. Cough frequency, duration, and severity were significantly (P < .0001) decreased at study end. Feasibility of aerosolized delivery improved with continued use (P = .05) with only 1 dog unable to accept inhaled medication.. This study supports the utility of fluticasone propionate by inhalation in management of cough in dogs with IAD and AWC.

Topics: Androstadienes; Animals; Asthma; Cough; Cross-Over Studies; Dog Diseases; Dogs; Double-Blind Method; Fluticasone; Glucocorticoids; Quality of Life

The clinical value of using digital tools to assess adherence and lung function in uncontrolled asthma is not known. We aimed to compare treatment decisions guided by digitally acquired data on adherence, inhaler technique, and peak flow with existing methods.. A 32-week prospective, multicentre, single-blinded, parallel, randomly controlled trial was done in ten severe asthma clinics across Ireland, Northern Ireland, and England. Participants were 18 years or older, had uncontrolled asthma, asthma control test (ACT) score of 19 or less, despite treatment with high-dose inhaled corticosteroids, and had at least one severe exacerbation in the past year despite high-dose inhaled corticosteroids. Patients were randomly assigned in a 1:1 ratio to the active group or the control group, by means of a computer-generated randomisation sequence of permuted blocks of varying sizes (2, 4, and 6) stratified by fractional exhaled nitric oxide (FeNO) concentration and recruitment site. In the control group, participants were masked to their adherence and errors in inhaler technique data. A statistician masked to study allocation did the statistical analysis. After a 1-week run-in period, both groups attended three nurse-led education visits over 8 weeks (day 7, week 4, and week 8) and three physician-led treatment adjustment visits at weeks 8, 20, and 32. In the active group, treatment adjustments during the physician visits were informed by digital data on inhaler adherence, twice daily digital peak expiratory flow (ePEF), patient-reported asthma control, and exacerbation history. Treatment was adjusted in the control group on the basis of pharmacy refill rates (a measure of adherence), asthma control by ACT questionnaire, and history of exacerbations and visual management of inhaler technique. Both groups used a digitally enabled Inhaler Compliance Assessment (INCA) and PEF. The primary outcomes were asthma medication burden measured as proportion of patients who required a net increase in treatment at the end of 32 weeks and adherence rate measured in the last 12 weeks by area under the curve in the intention-to-treat population. The safety analyses included all patients who consented for the trial. The trial is registered with ClinicalTrials.gov, NCT02307669 and is complete.. Between Oct 25, 2015, and Jan 26, 2020, of 425 patients assessed for eligibility, 220 consented to participate in the study, 213 were randomly assigned (n=108 in the active group; n=105 in the control group) and 200 completed the study (n=102 in the active group; n=98 in the control group). In the intention-to-treat analysis at week 32, 14 (14%) active and 31 (32%) control patients had a net increase in treatment compared with baseline (odds ratio [OR] 0·31 [95% CI 0·15-0·64], p=0·0015) and 11 (11%) active and 21 (21%) controls required add-on biological therapy (0·42 [0·19-0·95], p=0·038) adjusted for study site, age, sex, and baseline FeNO. Three (16%) of 19 active and 11 (44%) of 25 control patients increased their medication from fluticasone propionate 500 μg daily to 1000 μg daily (500 μg twice a day; adjusted OR 0·23 [0·06-0·87], p=0·026). 26 (31%) of 83 active and 13 (18%) of 73 controls reduced their medication from fluticasone propionate 1000 μg once daily to 500 μg once daily (adjusted OR 2·43 [1·13-5·20], p=0·022. Week 20-32 actual mean adherence was 64·9% (SD 23·5) in the active group and 55·5% (26·8) in the control group (between-group difference 11·1% [95% CI 4·4-17·9], p=0·0012). A total of 29 serious adverse events were recorded (16 [55%] in the active group, and 13 [45%] in the control group), 11 of which were confirmed as respiratory. None of the adverse events reported were causally linked to the study intervention, to the use of salmeterol-fluticasone inhalers, or the use of the digital PEF or INCA.. Evidence-based care informed by digital data led to a modest improvement in medication adherence and a significantly lower treatment burden.. Health Research Board of Ireland, Medical Research Council, INTEREG Europe, and an investigator-initiated project grant from GlaxoSmithKline.

Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Double-Blind Method; Fluticasone; Humans; Lung; Medication Adherence; Nebulizers and Vaporizers; Prospective Studies; Treatment Outcome

In 2019, the U.S. Food and Drug Administration (FDA) approved the first generic maintenance inhaler for asthma and chronic obstructive pulmonary disease (COPD). The inhaler, Wixela Inhub (fluticasone-salmeterol; Viatris), is a substitutable version of the dry powder inhaler Advair Diskus (fluticasone-salmeterol; GlaxoSmithKline). When approving complex generic products like inhalers, the FDA applies a special "weight-of-evidence" approach. In this case, manufacturers were required to perform a randomized controlled trial in patients with asthma but not COPD, although the product received approval for both indications.. To compare the effectiveness and safety of generic (Wixela Inhub) and brand-name (Advair Diskus) fluticasone-salmeterol among patients with COPD treated in routine care.. A 1:1 propensity score-matched cohort study.. A large, longitudinal health care database.. Adults older than 40 years with a diagnosis of COPD.. Incidence of first moderate or severe COPD exacerbation (effectiveness outcome) and incidence of first pneumonia hospitalization (safety outcome) in the 365 days after cohort entry.. Among 45 369 patients (27 305 Advair Diskus users and 18 064 Wixela Inhub users), 10 012 matched pairs were identified for the primary analysis. Compared with Advair Diskus use, Wixela Inhub use was associated with a nearly identical incidence of first moderate or severe COPD exacerbation (hazard ratio [HR], 0.97 [95% CI, 0.90 to 1.04]) and first pneumonia hospitalization (HR, 0.99 [CI, 0.86 to 1.15]).. Follow-up times were short, reflecting real-world clinical practice. The possibility of residual confounding cannot be completely excluded.. Use of generic and brand-name fluticasone-salmeterol was associated with similar outcomes among patients with COPD treated in routine practice.. National Heart, Lung, and Blood Institute.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Bronchodilator Agents; Cohort Studies; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Pneumonia; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate

This study was to evaluate the clinical efficacy and safety of fluticasone/ salmeterol inhalation powder plus Huaiqihuang Granules for children with cough variant asthma (CVA). From June 2019 to May 2021, 60 children with CVA were hospitalized to the Pediatrics Department of Cangzhou Central Hospital and randomized to the observation (fluticasone/salmeterol inhalation powder plus huaiqihuang granules) and control group (fluticasone/salmeterol inhalation powder) using the random number table method. The outcome measures include clinical efficacy, forced vital capacity (FVC), forced expiratory volume per second (FEV1), peak expiratory flow (PEF), FeNO, high-sensitivity C-reactive protein (hs-CRP), interleukin-17 (IL-17) and IL-23, airway anatomical indicators and T lymphocyte subsets levels. Both groups exhibited remarkable improvements in FVC, FEV1, PEF and FeNO and hs-CRP, IL-17 and IL-23, with higher FVC, FEV1 and PEF and lower FeNO, hs-CRP, IL-17 and IL-23 in the observation group (all P<0.05). Significantly higher levels of CD4+ and CD4+/CD8+ were observed in the observation group versus control group, but lower airway wall thickness, basement membrane thickness, total airway wall area and CD8+ in the observation group (all P<0.05). Fluticasone/salmeterol inhalation powder plus Huaiqihuang Granules improves lung function, FeNO and airway inflammation in children with CVA and boosts cellular and humoral immune function.

Topics: Asthma; C-Reactive Protein; Child; Cough; Fluticasone; Humans; Interleukin-17; Interleukin-23; Powders; Salmeterol Xinafoate; Treatment Outcome

Growth impairment is a known adverse event (AE) of corticosteroids in children. This study aimed to assess the effect of once-daily (QD) inhaled fluticasone furoate (FF) versus placebo on growth velocity over 1 year in prepubertal children with well-controlled asthma.. This randomized, double-blind, parallel-group, placebo-controlled, multicenter study (NCT02889809) included prepubertal children, aged 5 to <9 years (boys), and 5 to <8 years (girls), with ≥6 months' asthma history. Children received inhaled placebo QD plus background open-label montelukast QD for a 16-week run-in period and were then randomized 1:1 to receive inhaled FF 50 μg QD or placebo QD (whilst continuing background open-label montelukast) for a 52-week treatment period. The primary endpoint was the difference in growth velocity (cm/year) over the treatment period. Other growth endpoints were measured, as were incidence of AEs and asthma exacerbation. Growth analyses included all intent-to-treat (ITT) participants with ≥3 post-randomization, on-treatment clinic visit height assessments (GROWTH population).. Of 644 children in the run-in period, 477 (mean age 6.2 years, 63% male) entered the 52-week treatment period (ITT population: FF N = 238, placebo N = 239; GROWTH population: N = 457 [FF N = 231; placebo N = 226]). The least-squares mean difference in growth velocity for FF versus placebo was -0.160 cm/year (95% confidence interval: -0.462, 0.142). There were no new safety signals.. Over 1 year, FF 50 μg QD had a minimal effect on growth velocity versus placebo, with no new safety signals.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Female; Fluticasone; Humans; Male; Treatment Outcome

Steroid resistance in asthma has been associated with neutrophilic inflammation and severe manifestations of the disease. Macrolide add-on therapy can improve the quality of life and the exacerbation rate in refractory cases, possibly with greater effectiveness in neutrophilic phenotypes. The mechanisms leading to these beneficial effects are incompletely understood and whether macrolides potentiate the modulation of bronchial remodeling induced by inhaled corticosteroids (ICS) is unknown. The objective of this study was to determine if adding azithromycin to ICS leads to further improvement of lung function, airway inflammation and bronchial remodeling in severe asthma. The combination of azithromycin (10 mg/kg q48h PO) and inhaled fluticasone (2500 µg q12h) was compared to the sole administration of fluticasone for five months in a randomized blind trial where the lung function, airway inflammation and bronchial remodeling (histomorphometry of central and peripheral airways and endobronchial ultrasound) of horses with severe neutrophilic asthma were assessed. Although the proportional reduction of airway neutrophilia was significantly larger in the group receiving azithromycin, the lung function and the peripheral and central airway smooth muscle mass decreased similarly in both groups. Despite a better control of airway neutrophilia, azithromycin did not potentiate the other clinical effects of fluticasone.

Topics: Administration, Inhalation; Airway Remodeling; Animals; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchodilator Agents; Drug Therapy, Combination; Female; Fluticasone; Horse Diseases; Horses; Male; Neutrophils

Fluticasone furoate/vilanterol trifenatate (FF/VI) is an inhaled therapy for the treatment of asthma, with a prolonged duration of anti-inflammatory and bronchodilatory action. This study investigated the global metabolomic and lipidomic profile following treatment with FF/VI or placebo and assessed whether changes correlated with exhaled nitric oxide levels as a measure of airway inflammation.. This was a single-center, randomized, double-blind, placebo-controlled, two-period, crossover, repeat-dose study. Adults with asthma (forced expiratory volume in 1 s ≥ 60% predicted; fraction of exhaled nitric oxide [FeNO] > 40 parts per billion) received once-daily FF/VI 100 µg/25 µg or placebo for 14 days, followed by a 21-day washout period. Serum samples were taken at pre-dose (T1), and 15 and 21 days (T2 and T3, respectively) post dose in each period. The metabolomic and lipidomic profiles were analyzed by liquid chromatography with tandem mass spectrometry and polar liquid chromatography platforms, and ions were matched to a library of standards for metabolite identification and quantification. FeNO values at each timepoint were evaluated for correlations with the biochemical data.. Of 27 randomized participants (mean age 24.5 years, 63% male), 26 provided serum samples for metabolomic analysis. A total of 1969 metabolites were identified, 1634 of which corresponded to a named structure in a reference library. Treatment-related changes in the metabolome were generally subtle, with a modest increase in metabolite perturbations across timepoints. The percentage of metabolites with significant changes (p < 0.05 for all) (increases↑/decreases↓) versus placebo were: 2.1% (1.1%↑/1.0%↓), 6.7% (0.46%↑/6.2%↓) and 11.8% (0.86%↑/10.9%↓) at T1, T2 and T3, respectively. Treatment with FF/VI reduced FeNO levels by 60%, whereas the systemic intermediates involved in NO biosynthesis remained unaffected. Evidence of systemic anti-inflammatory activity was seen in complex lipid pathways, suggesting reduced phospholipase-A2 activity, but without downstream impact on free fatty acids or inflammatory mediators. Consistent with the pathogenesis of asthma, there was evidence of higher fatty acid β-oxidation and lower glycolysis in the placebo arm; this pattern was reversed in the treatment arm.. Despite the prolonged airway anti-inflammatory action of FF/VI, this was accompanied by only subtle systemic metabolomic and lipidomic changes. Trial registration Prospectively registered on ClinicalTrials.gov registry number NCT02712047.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Benzyl Alcohols; Chlorobenzenes; Fatty Acids, Nonesterified; Female; Fluticasone; Humans; Inflammation; Inflammation Mediators; Male; Nitric Oxide; Phospholipases; Young Adult

The objective of this study was to compare inhaled glucocorticoids with oral glucocorticoids for treatment of naturally occurring feline asthma. Secondary goals were to evaluate serum allergy testing results in cats and to quantify the effect of an inhaled glucocorticoid (fluticasone) on glucose homeostasis. Nine cats with asthma were enrolled on the basis of clinical signs, thoracic radiographic findings, and airway eosinophilia. Cats were randomized and 4 cats were treated with oral glucocorticoids and 5 cats with inhaled glucocorticoids, with a 7-day course of oral glucocorticoids overlapping at the start of therapy. Cats were evaluated at baseline and at 8 wk with thoracic radiographs, bronchoalveolar lavage, lung function testing, and fructosamine levels. Serum allergen panels were evaluated. All cats were clinically normal after treatment and had significantly improved airway eosinophilia and decreased nucleated cell count. No improvement was seen in radiographic changes after treatment with either therapy. Oral, but not inhaled glucocorticoids, caused a decrease in airway resistance, although cats in the inhaled group had a higher baseline resistance than those in the oral group. Fructosamine levels did not change with treatment. Fifty percent of cats tested positive for immunoglobulin E (IgE) antibodies. Asthma is a heterogeneous condition; individual cats responded well to both oral and inhaled glucocorticoids. Ongoing evaluation of the potential underlying causes and therapeutic options is warranted with a larger group of cats.. L’objectif de l’étude était de comparer le traitement de l’asthme félin avec des glucocorticoïdes inhalés et administrés par voie entérale. Les objectifs secondaires étaient d’évaluer les résultats de tests d’allergies de chats atteints d’asthme félin et de quantifier l’effet d’un glucocorticoïde inhalé (fluticasone) sur l’homéostasie du glucose. Neuf chats atteints d’asthme félin ont été recrutés selon les signes cliniques, les trouvailles radiographiques et les évaluations cytologiques des voies aériennes (éosinophilie). Les chats ont été randomisés. Quatre chats ont été traités avec des glucocorticoïdes par voie entérale et cinq chats avec des glucocorticoïdes inhalés dont les 7 premiers jours ont été associés à l’administration de glucocorticoïdes par voie orale. Les chats ont initialement été évalués au moment du recrutement et puis à huit semaines avec des radiographies thoraciques, lavage bronchoalvéolaire, tests de fonction pulmonaire et dosage de la fructosamine. Des tests sériques d’allergènes ont également été évalués. Tous les chats ont eu une résolution des signes cliniques après le traitement et avaient une amélioration significative du compte éosinophilique du LBA. Aucune amélioration des lésions radiographiques suivant le traitement soit inhalé ou entéral n’a été observée. Seuls les glucocorticoïdes entéraux ont causés une diminution de la résistance des voies respiratoires. Toutefois les chats du groupe de traitement de glucocorticoïdes inhalés avaient, avant l’initiation du traitement, une résistance pulmonaire plus importante. Les niveaux de fructosamine n’ont pas changé significativement, et ce dans les deux groupes de traitement. 50 % des chats ont testé positif pour des anticorps IgE contre des allergènes inhalés communs. L’asthme est une entité clinique hétérogène; les chats ont individuellement bien répondu autant au traitement inhalé qu’au traitement entéral. L’étude des potentielles causes sous-jacente et des différentes options thérapeutiques sont recommandées dans une population plus grande de chats.(Traduit par les auteurs).

Topics: Administration, Inhalation; Administration, Oral; Animals; Asthma; Cat Diseases; Cats; Female; Fluticasone; Male; Pilot Projects; Prednisolone

Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Drug Combinations; Dry Powder Inhalers; Female; Fluticasone; Formoterol Fumarate; Humans; India; Male; Middle Aged; Peak Expiratory Flow Rate; Prospective Studies; Surveys and Questionnaires

Patients with asthma uncontrolled on inhaled corticosteroids may benefit from umeclidinium (UMEC), a long-acting muscarinic antagonist.. This Phase IIb, double-blind study included patients with reversible, uncontrolled/partially-controlled asthma for ≥6 months, receiving ≥100 mcg/day fluticasone propionate (or equivalent) for ≥12 weeks. Following a 2-week run-in on open-label fluticasone furoate (FF) 100 mcg, patients were randomised (1:1:1) to receive UMEC 31.25 mcg, UMEC 62.5 mcg or placebo on top of FF 100 mcg once-daily for 24 weeks. As-needed salbutamol was provided. Primary and secondary endpoints were change from baseline in clinic trough forced expiratory volume in 1 s (FEV. The intent-to-treat population comprised 421 patients (UMEC 31.25 mcg: n =139, UMEC 62.5 mcg: n =139, placebo: n =143). UMEC 31.25 mcg and 62.5 mcg demonstrated significantly greater improvements from baseline in clinic trough FEV. UMEC is a highly effective bronchodilator that leads to improved lung function when administered as a single bronchodilator on top of FF in subjects with fully reversible, uncontrolled/partially-controlled moderate asthma. These data support a favourable benefit/risk profile for UMEC (31.25 mcg and 62.5 mcg).. GSK study ID: 205832; Clinicaltrials.gov ID: NCT03012061.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Therapy, Combination; Drug Tolerance; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Quinuclidines; Treatment Outcome

The combination drug of inhaled corticosteroid (ICS)/long-acting β2 agonist is being used as a long-term control medication for pediatric asthma patients for those who are poorly controlled by ICS alone. Long-term efficacy and safety of Fluticasone propionate/formoterol fumarate hydrate (FP/FM) was evaluated in pediatric patients with bronchial asthma.. Two inhales of FP/FM (50/5μg) at one time, twice daily were administered for 24 weeks to Japanese asthma patients aged 5 to ＜16 years who had asthma symptoms during the observation period while using the same dosage of ICS during a certain period of time. Adverse drug reactions, morning peak flow (mPEF) and asthma symptoms were evaluated 24 weeks after administration.. FP/FM was administered to 53 subjects. 52 subjects completed the 24 week administration. The incidence of adverse drug reactions was 9.4% (5 of 53), and all of the adverse drug reactions were mild. The mPEF increased from the starting value and was maintained through the treatment period. The average change from baseline in the mPEF after 24 weeks of treatment was 21.39±2.93L/min (Least squares mean±standard error). Changes in asthma symptoms were similar to that of morning peak flow.. It was considered that FP/FM could be useful for long-term control of pediatric asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Aerosols; Asthma; Bronchodilator Agents; Child; Child, Preschool; Drug Combinations; Fluticasone; Formoterol Fumarate; Humans; Japan; Treatment Outcome

Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.. We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry.. When quintupling the dose of fluticasone (to 250 μg twice a day) was compared with adding salmeterol (50 μg twice a day) and doubling the fluticasone (to 100 μg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age.. In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Black or African American; Bronchodilator Agents; Child; Child, Preschool; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Fluticasone; Glucocorticoids; Humans; Male; Prospective Studies; Salmeterol Xinafoate

The airway microbiome has an important role in asthma pathophysiology. However, little is known on the relationships between the airway microbiome of asthmatic children, loss of asthma control, and severe exacerbations. Here we report that the microbiota's dynamic patterns and compositions are related to asthma exacerbations. We collected nasal blow samples (n = 319) longitudinally during a clinical trial at 2 time-points within one year: randomization when asthma is under control, and at time of early loss of asthma control (yellow zone (YZ)). We report that participants whose microbiota was dominated by the commensal Corynebacterium + Dolosigranulum cluster at RD experience the lowest rates of YZs (p = 0.005) and have longer time to develop at least 2 episodes of YZ (p = 0.03). The airway microbiota have changed from randomization to YZ. A switch from the Corynebacterium + Dolosigranulum cluster at randomization to the Moraxella- cluster at YZ poses the highest risk of severe asthma exacerbation (p = 0.04). Corynebacterium's relative abundance at YZ is inversely associated with severe exacerbation (p = 0.002).

Topics: Administration, Inhalation; Asthma; Carnobacteriaceae; Child; Child, Preschool; Female; Fluticasone; Host Microbial Interactions; Humans; Male; Microbiota; Moraxella; Nasal Mucosa; Prospective Studies; Severity of Illness Index; Staphylococcus; Streptococcus; Symbiosis; Symptom Flare Up; Treatment Outcome

To evaluate retinal nerve fiber layer thickness (RNFLT), ganglion cell layer thickness (GCLT), subfoveal choroidal thickness (SFCT), and central retinal thickness (CRT) in asthmatic children who were under inhaled corticosteroid treatment by using Swept-Source Optical Coherence Tomography (SS-OCT).. Fifty-three children were prospectively analyzed in the study. Group 1 included 31 asthmatic children and group 2 included 22 healthy children. Asthmatic children received a dose 250 μg daily of inhaled fluticasone propionate (Flexotide, GlaxoSmithKline, Middlesex, UK). Allergy parameters including, exposure to smoke, eosinophil count, percentage of eosinophils, immunoglobuline (Ig) E levels, number of asthma attacks, number of sensitivity to allergens and follow-up time were recorded. The RNFLT, GCLT, SFCT, and CRT were analyzed with SS-OCT and the data were compared between the groups.. There were 13 girls (41.9%) and 18 boys (58.1%) in group 1 and 13 girls (59.1%) and 9 boys (40.9%) in group 2 (p = 0.22). The mean age was 9.3 ± 2.2 years in group 1 and 9.9 ± 1.5 years in group 2 (p = 0.08). The mean CRT (239.26 ± 34.56 µm versus 226.82 ± 26.23 µm, p = 0.22) and mean SFCT (273.97 ± 40.95 µm versus 280.41 ± 32.78 µm, p = 0.54) did not significantly differ between the groups. The superior, inferior, and average RNFLT were significantly lower in group 1 than group 2 (p < 0.05). There were significant correlations between total corticosteroid dose and RNFLT (p < 0.05) and between IgE levels and GCLT (p < 0.05).. The SS-OCT revealed that asthmatic children under inhaled corticosteroid treatment have lower RNFLT than healthy subjects.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Child; Eosinophilia; Female; Fluticasone; Humans; Immunoglobulin E; Male; Skin Tests; Tomography, Optical Coherence

Loss of bronchoprotection (LOBP) with a regularly used long-acting β. We sought to determine whether alendronate can reduce LABA-associated LOBP in inhaled corticosteroid (ICS)-treated patients.. We conducted a randomized, double-blind, placebo-controlled, parallel-design, proof-of-concept trial. Seventy-eight participants with persistent asthma receiving 250 μg of fluticasone twice daily for 2 weeks were randomized to receive alendronate or placebo while initiating salmeterol for 8 weeks. Salmeterol-protected methacholine challenges (SPMChs) and PBMC B2AR numbers (radioligand binding assay) and signaling (cyclic AMP ELISA) were assessed before randomization and after 8 weeks of ICS plus LABA treatment. LOBP was defined as a more than 1 doubling dose reduction in SPMCh PC. This study did not find evidence that alendronate reduces LABA-associated LOBP, which relates to the occurrence of LOBP in only one third of participants. LOBP appears to be less common than presumed in concomitant ICS plus LABA-treated asthmatic patients. B2AR downregulation measured in PBMCs does not appear to reflect LOBP.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Alendronate; Asthma; Double-Blind Method; Female; Fluticasone; Humans; Male; Proof of Concept Study; Receptors, Adrenergic, beta-2; Salmeterol Xinafoate

To study the clinical effect of different combinations of fluticasone propionate (Flu), montelukast sodium (Mon) and ketotifen (Ket) in the treatment of children with cough variant asthma (CVA).. A total of 280 children with CVA who were admitted to the department of respiratory medicine from June 2015 to January 2018 were randomly divided into Flu+Mon+Ket, Flu+Mon, Flu+Ket, Mon+Ket, Flu, Mon and Ket groups, with 40 children in each group. The children in each group were given corresponding drug(s), and the course of treatment was 3 months for all groups. The condition of cough, cough symptom score, pulmonary function and adverse drug reactions were evaluated after 2 and 3 months of treatment. The children were followed up to observe recurrence.. After treatment, cough symptom score tended to decrease in all 7 groups, with increases in percentage of forced expiratory volume in 1 second (FEV1%) and percentage of predicted peak expiratory flow (PEF%). After 2 months of treatment, the Flu+Mon+Ket group had a significantly lower cough symptom score and significantly higher FEV1% and PEF% than the other groups (P<0.05). After 2 and 3 months of treatment, the Ket group had a significantly higher cough symptom score and significantly lower FEV1% and PEF% than the other groups (P<0.05). After 3 months of treatment, there were no significant differences in cough symptom score, FEV1% and PEF% among the other groups (P>0.05). There was a low incidence rate of adverse events in all 7 groups, and there was no significant difference among the 7 groups (P>0.05). The Ket group had a significantly higher recurrence rate of cough than the other groups (P<0.001), while there was no significant difference in this rate among the other groups (P>0.0024).. For children with CVA, a combination of Flu, Mon and Ket has a better clinical effect than a combination of two drugs and a single drug at 2 months of treatment and is safe. After 3 months of treatment, Flu or Mon alone has a similar effect to drug combination. Ket alone has a poor clinical effect and a high recurrence rate after drug withdrawal.

Topics: Acetates; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Cough; Cyclopropanes; Drug Combinations; Fluticasone; Humans; Ketotifen; Quinolines; Sulfides

In 2004, the landmark Gaining Optimal Asthma Control (GOAL) study demonstrated that most patients can achieve asthma control through sustained treatment and that adding a long-acting β. To evaluate the efficacy of fluticasone propionate and salmeterol and fluticasone propionate alone in achieving and maintaining asthma control, as derived from the Global Initiative for Asthma (GINA) 2016 report.. In total, 3416 patients were stratified by prior medication (ICS-naive [stratum 1], low-dose ICS [stratum 2], or medium-dose ICS [stratum 3]) and randomized to receive fluticasone propionate and salmeterol or fluticasone propionate. The primary end point was the proportion of patients achieving well-controlled or partly controlled asthma; secondary end points included the proportion of patients achieving well-controlled asthma. Control was evaluated during the last 4 weeks of each dose titration.. In all strata, more patients achieved well-controlled or partly controlled asthma with fluticasone propionate and salmeterol vs fluticasone propionate alone (stratum 1: 91% vs 85%; P = .003; stratum 2: 86% vs 82%; P = .07; and stratum 3: 76% vs 66%; P < .001), as well as patients with well-controlled asthma (stratum 1: 64% vs 56%; P = .005; stratum 2: 59% vs 41%; P < .001; and stratum 3: 40% vs 22%; P < .001).. A markedly higher proportion of patients with uncontrolled asthma in each stratum achieved control according to GINA 2016 criteria compared with the original study criteria. The proportion of patients achieving control remained greater with fluticasone propionate and salmeterol than with fluticasone propionate alone.

Topics: Adrenergic beta-2 Receptor Agonists; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Therapy, Combination; Fluticasone; Humans; Salmeterol Xinafoate

Several gene variants are associated with a response to an inhaled corticosteroids (ICSs) treatment in patients with bronchial asthma. A variant of the glucocorticoid-induced transcript 1 (GLCCI1) genes has previously been associated with decreased lung function improvement upon treatment with ICSs in patients with bronchial asthma. Another report has also demonstrated that this genetic biomarker did not influence the change in flow volume in 1 second. However, no studies have considered the treatment content and the GLCCI1 variants. We were able to determine the relationship between the pulmonary function and clinical features and the variant of the GLCCI1 in Japanese asthmatic patients receiving long-term ICS treatment.. In this study, 405 patients with bronchial asthma, who were receiving ICS and living in Japan, were recruited, genotyped and underwent pulmonary function tests. To identify the GLCCI1 protein expression cells, endobronchial biopsy specimens were examined.. We found that the pulmonary function was not significantly different in the homozygotes compared to the wild types. Also, the homozygotes increased the risk of a sustained step-up of the asthma treatment when compared to the wild type and heterozygotes. GLCCI1-positive cells were localized to the bronchial epithelial cells. The amount of GLCCI1 protein that cultured epithelial cells harboring GLCCI1 variants produced was less than the GLCCI1 wild type in the presence of a corticosteroid.. A worsening of pulmonary function caused by GLCCI1 variants could be prevented due to recently used medications based on new action mechanisms.

Topics: Anti-Inflammatory Agents; Asthma; Bronchoscopy; Budesonide; Cells, Cultured; Female; Fluticasone; Gene Expression Regulation; Genetic Variation; Genotype; Glucocorticoids; Humans; Immunoblotting; Immunohistochemistry; Male; Middle Aged; Prospective Studies; Real-Time Polymerase Chain Reaction; Receptors, Glucocorticoid; Respiratory Function Tests; Respiratory Mucosa; RNA; Treatment Outcome

To assess the efficacy and safety of fluticasone propionate (Fp) and Fp/salmeterol (FS) administered via a novel multidose dry powder inhaler (MDPI) that is easy to use correctly in asthma patients.. This phase-3, multicenter, double-blind, parallel-group study evaluated asthmatic patients (≥12 years of age) previously treated with either low- or mid-dose inhaled corticosteroids (ICSs) or ICS/long-acting beta agonists. After a 14- to 21-day run-in, patients were randomized to Fp MDPI 50 mcg, Fp MDPI 100 mcg, FS MDPI 50/12.5 mcg, FS MDPI 100/12.5 mcg, or placebo twice daily for 12 weeks. Change from baseline in forced expiratory volume in 1 second (FEV. The full analysis and serial spirometry subset included 640 and 312 patients, respectively. At week 12, FS MDPI significantly improved FEV. Pulmonary function was significantly improved with Fp MDPI and FS MDPI vs placebo and FS MDPI vs Fp MDPI. Active treatments had a safety profile comparable to placebo.

Topics: Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Dry Powder Inhalers; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Spirometry; Treatment Outcome; Young Adult

For more than a decade, urinary free cortisol corrected for creatinine (OUFCC) has been used to assess the systemic bioactivity of inhaled corticosteroids in children with asthma. Paediatric normative ranges, however, have not been established. The aim of the present study was to define a preliminary range for OUFCC in Tanner stage 1 children.. A post hoc analysis was performed of 26 Tanner stage one children (aged 5-11 years) with mild asthma only requiring prn (pro re nata) treatment with short-acting β. Twenty-six children contributed 41 OUFCC values. The geometric mean OUFCC was 9.0 nmol/mmol (95% PI: 3.6, 22.7 nmol/mmol).. The OUFCC preliminary normative range was 3.6 to 22.7 nmol/mmol in Tanner stage one children. A larger study in healthy children is warranted to confirm these findings and to assess potential differences in OUFCC across developmental stages and age groups, and by gender and race.. 2013-004719-32, CLINICALTRIALS.. NCT02063139.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Creatinine; Cross-Over Studies; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Hydrocortisone; Male; Pilot Projects; Reference Values

Topics: Administration, Inhalation; Adult; Aged; Asthma; Benzyl Alcohols; Chlorobenzenes; Delayed-Action Preparations; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; United Kingdom

Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma.. We conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma.. A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group.. In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN15441965 .).

Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; Kaplan-Meier Estimate; Male; Proportional Hazards Models; Self-Management

Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited.. We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids.. The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06).. In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).

Topics: Administration, Inhalation; Albuterol; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Growth; Humans; Male; Peak Expiratory Flow Rate

Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Asthmatic Agents; Arginine; Asthma; Biomarkers; Child, Preschool; Female; Fluticasone; Glutathione; Humans; Infant; Male; Ornithine

In vitro and scintigraphic studies have suggested that effectiveness of metered-dose inhalers (MDI) with nonvalved spacers (NVS) is similar to that of MDI with valved holding chambers (VHC). Nevertheless, there are no clinical studies that compare these techniques in long-term treatment with inhaled steroids in young children with recurrent wheezing and risk factors for asthma.. To compare the efficacy of a long-term treatment with Fluticasone Propionate administered by an MDI through both type of spacers, with and without valves, in young children with recurrent wheezing and risk factors for asthma.. Outpatient children (6 to 20 months old) with recurrent wheezing and risk factors for asthma were randomized to receive a 6-month treatment with metered-dose inhaler (MDI) of Fluticasone Propionate 125 mcg BID through an NVS or through a VHC. Parents recorded daily their child's respiratory symptoms and rescue medication use.. Long-term treatment with inhaled steroids administered by MDI and NVS is less effective than such treatment by MDI and VHC in infants with recurrent wheezing and risk factors for asthma.

Topics: Albuterol; Asthma; Bronchodilator Agents; Female; Fluticasone; Humans; Infant; Inhalation Spacers; Male; Respiratory Sounds

To analyse the efficacy of fluticasone propionate (FP) alone and combined with salmeterol (SAL) in achieving guideline-defined asthma control in Asian patients.. A post hoc analysis of the GOAL study in which patients were stratified by prior-medication use into inhaled corticosteroid (ICS)-naïve (Stratum [S] 1), low-dose ICS (S2), and medium-dose ICS (S3), and randomised to receive FP/SAL or FP. Doses were stepped-up every 12 weeks until Totally Controlled asthma or maximum dose was reached (PhI) and then maintained until study end (PhII). The primary endpoint was the proportion of patients achieving Well-Controlled asthma during PhI. Additional endpoints included Total Control and adverse events. Asian and non-Asian patients were analysed separately.. In Asian patients in PhI, 74% (n = 87/118) in S1 achieved Well-Controlled asthma with FP/SAL versus 74% (n = 89/121) with FP alone (p = 0.839); corresponding values were 76% (n = 81/107) versus 60% (n = 62/104; p = 0.005) in S2, and 58% (n = 59/102) versus 43% (n = 41/95; p = 0.015) in S3. More patients in all three strata achieved Totally Controlled asthma with FP/SAL versus FP alone. Control was achieved more rapidly and with lower ICS doses with FP/SAL versus FP. A high proportion of patients who achieved control during PhI maintained control during PhII. Similar trends were found in non-Asian patients. No new safety concerns were identified.. A greater proportion of Asian patients (S2 and S3, for Well-Controlled; all strata, for Totally Controlled) achieved guideline-defined asthma control with FP/SAL versus FP alone. High proportions of Asian patients in S1 achieved Well-Controlled asthma in both treatment groups.

Topics: Adrenal Cortex Hormones; Adult; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Humans; Internationality; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Quality of Life; Respiratory Function Tests; Salmeterol Xinafoate; Severity of Illness Index; Treatment Outcome

Airway hyperresponsiveness (AWHR), expressed as hypersensitivity (PC. To determine whether dexamethasone (DEX) (0.05 mg/kg IM q24h) and inhaled fluticasone (FLUT) (3,000 μg q12h) administered by inhalation are effective in decreasing AWHR, lung inflammation, and clinical signs in horses with IAD.. A randomized crossover study design was used. Eight horses with IAD were assigned to a treatment group with either DEX or FLUT. Measured outcomes included lung mechanics during bronchoprovocative challenges, bronchoalveolar lavage fluid (BALF) cytology, and scoring of clinical signs during exercise.. Dexamethasone and FLUT abolished the increase in R. Both DEX and FLUT treatments significantly inhibit airway hypersensitivity and hyperreactivity in horses with IAD. There are no significant effects on the clinical signs or the number of inflammatory cells (except lymphocytes) in BALF. The treatments have no residual effect 3 weeks after discontinuation.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Cross-Over Studies; Dexamethasone; Female; Fluticasone; Horse Diseases; Horses; Male; Respiratory Function Tests; Respiratory Hypersensitivity

A novel, inhalation-driven, multidose dry powder inhaler (MDPI) has been developed, which allows for lower doses of fluticasone propionate (Fp) and Fp/salmeterol (FS) for the treatment of patients with asthma.. This phase III, multicenter, double-blind, parallel-group study (NCT02141854) evaluated the efficacy and safety of Fp MDPI and FS MDPI versus placebo MDPI.. Patients aged ≥12 years with persistent asthma who previously took an inhaled corticosteroid with or without a long-acting beta-agonist entered a 14- to 21-day run-in period, during which they received single-blind, low-dose Fp MDPI 50 μg (1 inhalation twice daily [b.i.d.]) and used albuterol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) for rescue. The patients who continued to meet eligibility criteria (N = 728) were randomized to Fp MDPI (100 or 200 μg), FS MDPI (100 μg/12.5 μg or 200 μg/12.5 μg), or placebo (1 inhalation b.i.d.). Primary efficacy end points were the change from baseline in forced expiratory volume in 1 second (FEV1) and the baseline-adjusted area under the FEV1 curve 12 hours after the dose at week 12. Secondary efficacy end points were A.M. peak expiratory flow, asthma symptom scores, albuterol HFA MDI use, time to patient withdrawal, Asthma Quality of Life scores, and time to 15% and 12% improvement from baseline in FEV1. Safety end points were monitored.. Fp MDPI and FS MDPI significantly improved both primary end points compared with placebo (p < 0.05). FS MDPI significantly improved both end points versus the corresponding Fp MDPI dose (p < 0.05), with improvement also greater for FS MDPI 100 μg/12.5 μg versus Fp MDPI 200 μg (p < 0.05). Both active treatments improved a variety of secondary end points and exhibited a safety profile consistent with the drug classes.. Delivery of Fp and FS via the novel MDPI provided significant clinical benefits and was well tolerated in patients with persistent asthma.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Bronchodilator Agents; Child; Dry Powder Inhalers; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Respiratory Function Tests; Retreatment; Risk Factors; Treatment Outcome; Young Adult

Evidence for management of asthma comes from closely monitored efficacy trials done in highly selected patient groups. There is a need for randomised trials that are closer to usual clinical practice.. We did an open-label, randomised, controlled, two-arm effectiveness trial at 74 general practice clinics in Salford and South Manchester, UK. Patients aged 18 years or older with a general practitioner's diagnosis of symptomatic asthma and on maintenance inhaler therapy were randomly assigned to initiate treatment with a once-daily inhaled combination of either 100 μg or 200 μg fluticasone furoate with 25 μg vilanterol or optimised usual care and followed up for 12 months. The primary endpoint was the percentage of patients who achieved an asthma control test (ACT) score of 20 or greater or an increase in ACT score from baseline of 3 or greater at 24 weeks (termed responders), in patients with a baseline ACT score less than 20 (the primary effectiveness analysis population). All effectiveness analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01706198.. Between Nov 12, 2012, and Dec 16, 2016, 4725 patients were enrolled and 4233 randomly assigned to initiate treatment with fluticasone furoate and vilanterol (n=2114) or usual care (n=2119). 1207 patients (605 assigned to usual care, 602 to fluticasone furoate and vilanterol) had a baseline ACT score greater than or equal to 20 and were thus excluded from the primary effectiveness analysis population. At week 24, the odds of being a responder were higher for patients who initiated treatment with fluticasone furoate and vilanterol than for those on usual care (977 [71%] of 1373 in the fluticasone furoate and vilanterol group vs 784 [56%] of 1399 in the usual care group; odds ratio [OR] 2·00 [95% CI 1·70-2·34], p<0·0001). At week 24, the adjusted mean ACT score increased by 4·4 points from baseline in patients initiated with fluticasone furoate and vilanterol, compared with 2·8 points in the usual care group (difference 1·6 [95% CI 1·3-2·0], p<0·0001). This result was consistent for the duration of the study. Pneumonia was uncommon, with no differences between groups; there was no difference in other serious adverse events between the groups.. In patients with a general practitioner's diagnosis of symptomatic asthma and on maintenance inhaler therapy, initiation of a once-daily treatment regimen of combined fluticasone furoate and vilanterol improved asthma control without increasing the risk of serious adverse events when compared with optimised usual care.. GlaxoSmithKline.

Topics: Administration, Inhalation; Adult; Ambulatory Care; Asthma; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Follow-Up Studies; General Practice; Humans; Male; Middle Aged; Prospective Studies; Respiratory Function Tests; Severity of Illness Index; Treatment Outcome; United Kingdom; Young Adult

Smoking is as prevalent in asthmatics as in the general population. Asthmatic smokers benefit less from inhaled corticosteroids (ICS) than non-smoking asthmatics, possibly due to more smoking-induced small airways disease. Thus targeting small airways may be important in treating asthmatic (ex-)smokers. We hypothesized that extrafine particle ICS improve small airways function more than non-extrafine particle ICS in asthmatic (ex-)smokers.. We performed an open-label, randomized, three-way cross-over study comparing extrafine beclomethasone (HFA-QVAR) to non-extrafine beclomethasone (HFA-Clenil) and fluticasone (HFA-Flixotide) in 22 smokers and 21 ex-smokers with asthma (?5 packyears).. Similar effectiveness in improving small airways function was found for extrafine and non-extrafine particle ICS treatment for asthmatic smokers and ex-smokers.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adrenal Cortex Hormones; Adult; Airway Remodeling; Asthma; Beclomethasone; Bronchial Provocation Tests; Cross-Over Studies; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Particle Size; Respiratory Function Tests; Smokers; Treatment Outcome

Despite reports of response to steroid inhaler in some clinically suspected asthma patients with negative methacholine challenge test (CSA/MCT-), treatment in these patients has not been prospectively studied.. We studied the role of a 12 week high dose inhaled fluticasone trial in CSA/MCT- patients.. After a 2 week run-in period, CSA/MCT-patients were treated with 12 weeks of Fluticasone propionate 1000 µg/day. The Asthma Control Test (ACT), numeric cough score (NCS) and bronchodilator use were compared with their pretreatment values.. Thirty-four of 42 CSA/MCT-patients completed the study. Mean pretreatment ACT score (pACT) was significantly increased after treatment (14.7 ± 3.37 to 20.9 ± 3.1, P < 0.001). Posttreatment values of daytime (1.0 ± 1.0) and night-time (0.6 ± 0.9) NCS decreased compared to their pretreatment values (2.8 ± 1.1 and 1.9 ± 1.3, respectively; P < 0.001). ACT score change (ΔACT) were significantly greater in those with pACT < 15 than in those ≥15 (P < 0.001) . Fifteen of 21 patients with ΔACT > 5 did not need to use bronchodilator for their symptom relief. Wheeze disappeared in all six patients with ΔACT > 5 after the trial. Six months after the study, steroid inhaler continued to be used by 72.2% of patients.. A significant portion of CSA/MCT- (especially those with pretreatment ACT score <15) respond to high dose fluticasone inhaler in terms of symptoms relief, disappearance of wheeze and need to bronchodilator use. ΔACT could not be predicted with any individual symptoms or signs before MCT, % FEV1 decline or symptoms during MCT and exhaled nitric oxide.

Topics: Administration, Inhalation; Adult; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Nebulizers and Vaporizers; Nitric Oxide

A novel, inhalation-driven, multidose dry powder inhaler (MDPI) eliminates the need to coordinate actuation with inhalation. To characterize dose response, efficacy, and safety of fluticasone propionate (Fp) MDPI, a dose-ranging study was conducted with placebo and active comparators.. This 12-week, double-blind, parallel-group study randomized patients aged ≥12 years with uncontrolled persistent asthma not previously treated with inhaled corticosteroid therapy (N = 622) to twice-daily treatment with Fp MDPI (12.5, 25, 50, or 100 µg), placebo MDPI, or open-label Fp dry powder inhaler (DPI) 100 µg. The primary efficacy endpoint was change from baseline over 12 weeks in trough (morning pre-dose and pre-rescue bronchodilator) forced expiratory volume in 1 second (FEV. Fp MDPI 25, 50, and 100 µg significantly improved change from baseline in trough FEV. In this study, Fp MDPI 25 and 50 µg provided comparable efficacy and safety to Fp DPI 100 µg, with lower systemic exposure.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Area Under Curve; Asthma; Bronchodilator Agents; Child; Dose-Response Relationship, Drug; Double-Blind Method; Dry Powder Inhalers; Female; Fluticasone; Humans; Male; Middle Aged; Respiratory Function Tests; Young Adult

Temporal fluctuations have been demonstrated in lung function and asthma control, but the effect of controller therapy on these fluctuations is unknown.. To determine if fluctuations in peak expiratory flow (PEF) are predictive of subsequent treatment failure and may be modified by controller therapy.. We applied detrended fluctuation analysis to once-daily PEF data from 493 participants in the LOCCS (Leukotriene Modifier Corticosteroid or Corticosteroid-Salmeterol) trial of the American Lung Association Airways Clinical Research Centers. We evaluated the coefficient of variation of PEF (CVpef) and the scaling exponent α, reflecting self-similarity of PEF, in relation to treatment failure from the run-in period of open-label inhaled fluticasone, and the treatment periods for subjects randomized to (1) continued twice daily fluticasone (F), (2) once daily fluticasone plus salmeterol (F + S), or (3) once daily oral montelukast (M).. The CVpef was higher in those with treatment failure in the F and F + S groups in the run-in phase, and all three groups in the treatment phase. α was similar between those with and without treatment failure in all three groups during the run-in phase but was higher among those with treatment failure in the F and F + S groups during the treatment phase. Participants in all three groups showed variable patterns of change in α leading up to treatment failure.. We conclude that increased temporal self-similarity (α) of more variable lung function (CVpef) is associated with treatment failure, but the pattern of change in self-similarity leading up to treatment failure is variable across individuals.

Topics: Acetates; Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Cyclopropanes; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Peak Expiratory Flow Rate; Quinolines; Salmeterol Xinafoate; Sulfides; Treatment Failure

Compositional differences in the bronchial bacterial microbiota have been associated with asthma, but it remains unclear whether the findings are attributable to asthma, to aeroallergen sensitization, or to inhaled corticosteroid treatment.. We sought to compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma, subjects with atopy but no asthma, and nonatopic healthy control subjects and to determine relationships of the bronchial microbiota to phenotypic features of asthma.. Bacterial communities in protected bronchial brushings from 42 atopic asthmatic subjects, 21 subjects with atopy but no asthma, and 21 healthy control subjects were profiled by using 16S rRNA gene sequencing. Bacterial composition and community-level functions inferred from sequence profiles were analyzed for between-group differences. Associations with clinical and inflammatory variables were examined, including markers of type 2-related inflammation and change in airway hyperresponsiveness after 6 weeks of fluticasone treatment.. The bronchial microbiome differed significantly among the 3 groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus, Neisseria, Fusobacterium, and Porphyromonas species and the Sphingomonodaceae family and depleted in members of the Mogibacteriaceae family and Lactobacillales order. Asthma-associated differences in predicted bacterial functions included involvement of amino acid and short-chain fatty acid metabolism pathways. Subjects with type 2-high asthma harbored significantly lower bronchial bacterial burden. Distinct changes in specific microbiota members were seen after fluticasone treatment. Steroid responsiveness was linked to differences in baseline compositional and functional features of the bacterial microbiome.. Even in subjects with mild steroid-naive asthma, differences in the bronchial microbiome are associated with immunologic and clinical features of the disease. The specific differences identified suggest possible microbiome targets for future approaches to asthma treatment or prevention.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Asthma; Bacteria; Bronchi; Female; Fluticasone; Humans; Hypersensitivity, Immediate; Male; Microbiota; Middle Aged; RNA, Bacterial; RNA, Ribosomal, 16S; Young Adult

Evaluate fluticasone propionate (Fp) using a novel, inhalation-driven, multidose dry powder inhaler (MDPI) in patients with severe persistent asthma, versus placebo MDPI and Fp dry powder inhaler (DPI).. Patients with persistent asthma despite use of high-dose inhaled corticosteroids were randomized to Fp MDPI 50, 100, 200, or 400 mcg; Fp DPI 250 mcg; or placebo MDPI twice daily for 12 weeks. The primary outcome measure was change from baseline in trough forced expiratory volume in 1 second (FEV. Six hundred forty patients were randomized; 459 (72%) completed the study. Numerical dose-related improvements in FEV. Clinical benefit observed with Fp MDPI in patients with persistent asthma was comparable to Fp DPI. Safety was reassuring with no unexpected findings. These results support further evaluation of Fp MDPI in asthma. (ClinicalTrials.gov identifier NCT01576718; EudraCT number 2010-023601-35).

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Area Under Curve; Asthma; Bronchodilator Agents; Child; Dose-Response Relationship, Drug; Double-Blind Method; Dry Powder Inhalers; Female; Fluticasone; Half-Life; Humans; Kaplan-Meier Estimate; Male; Metabolic Clearance Rate; Middle Aged; Respiratory Function Tests; Young Adult

Valved holding chambers (VHCs) are used in children to deliver pressurized metered dose inhalers (pMDI). In vitro data suggest that uncoordinated use decreases the amount of drug available for inhalation. We hypothesize that in an ex vivo study, the coordinated maneuver will deliver more drug than the uncoordinated one.. Thirty-two clinically stable asthmatic children, ages 5-8 years, completed the study. An aerosol filter was interposed between a small-volume nonelectrostatic VHC and a mouthpiece to capture the drug emitted by one puff of Flovent. [mean (99% confidence interval)] Filter dose was higher during coordinated technique 46% (43%-50%) than during uncoordinated technique 41% (37%-44%) (p < 0.001). Peak inspiratory flow and tidal volume were 23.2 L/min (21.3-25.1 L/min) and 281 mL (251-311 mL), respectively. Subjects required three breaths to empty the VHC in 96% of the tests.. Actuating the pMDI into a small-volume nonelectrostatic VHC during exhalation reduced by 11% the amount of fluticasone captured at the exit of the VHC. Asthmatic children (5-8 years old) need three or less breaths to empty the small-volume VHC (NCT01714063).

Topics: Administration, Inhalation; Aerosols; Asthma; Bronchodilator Agents; Child; Child, Preschool; Chromatography, High Pressure Liquid; Cross-Over Studies; Drug Delivery Systems; Equipment Design; Female; Fluticasone; Humans; Inhalation Spacers; Male; Metered Dose Inhalers; Single-Blind Method; Tidal Volume

Asthma is characterized by a complex interaction of inflammatory mediators. The prostaglandin D2 receptor, chemoattractant receptor-homologous molecule on Th2 cells (CRTH2), plays a pivotal role in the pathogenesis of allergic airway inflammation.. To ealuate the efficacy, safety, and pharmacokinetics of BI 671800, a CRTH2 antagonist, when added to inhaled corticosteroid therapy in adult patients with symptomatic asthma.. In this phase IIa, 12-week, randomized, double-blind, three-period, four-treatment, incomplete block crossover trial, BI 671800 was administered either as a single 400-mg dose in the morning (A.M.) or evening (P.M.), or 200 mg twice daily (A.M. and P.M.) versus placebo, together with fluticasone propionate (44 μg, two inhalations twice daily). The primary end point was the change from baseline in trough forced expiratory volume in 1 second percentage predicted after 4 weeks. The secondary end point was the change in Asthma Control Questionnaire score from baseline.. A total of 108 patients were randomized and treated. After 4 weeks, the adjusted mean (± SE) treatment differences for the primary end point versus placebo were 0.08 ± 0.62%, 0.28 ± 0.61%, and 0.67 ± 0.63% for BI 671800 at 200 mg twice daily, 400 mg A.M., and 400 mg P.M., respectively (not statistically significant). No statistically significant or clinically meaningful differences in the Asthma Control Questionnaire score were observed versus placebo. Each treatment was well tolerated.. BI 671800 at a dose of 400 mg administered for 4 weeks with fluticasone propionate did not provide clinical improvement in patients with asthma; reasons for this are unclear, but it may be due to insufficient inhibition of the CRTH2 receptor at the doses used.

Topics: Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Benzamides; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Pyrimidines; Receptors, Immunologic; Receptors, Prostaglandin; Treatment Outcome; Vital Capacity

Periostin is a biomarker of eosinophilic airway inflammation and may contribute to airway remodeling in asthma. The anti-inflammatory activity of inhaled corticosteroids (ICS) for asthma control is widely recognized. The aim of this study was to assess the effects of ICS on serum periostin levels and its relationships to inflammation and airway geometry.. Forty-two healthy controls and 20 patients with steroid-naïve asthma before and after treatment with fluticasone propionate (800 μg/day for 16 weeks) were examined. Serum periostin, lung function and inflammatory cell counts in sputum were measured. Airway dimensions were determined by quantitative computed tomography (total area of the airway (Ao), wall area (WA), wall thickness (T) and percentage wall area (WA%) ).. Serum periostin concentrations were significantly higher in patients with asthma than in controls. Periostin levels were correlated with airway wall thickness and sputum eosinophilia and inversely correlated with airflow limitation in asthma. ICS significantly decreased serum periostin (P < 0.01), decreased WA corrected for body surface area (WA/BSA, P < 0.05), T/√BSA (P < 0.01) and WA% (P < 0.01), reduced the percentage of sputum eosinophils (P < 0.01) and improved airflow limitation. The decrease in serum periostin levels was associated with an increased per cent predicted forced expiratory volume in 1 s (r = -0.64, P < 0.01), decreased WA/BSA (r = 0.46, P < 0.05) and decreased sputum eosinophils (r = 0.71, P < 0.01).. Serum periostin levels respond partially to ICS and may reflect a reduction in airway inflammation and wall thickening in asthma.

Topics: Administration, Inhalation; Adult; Airway Remodeling; Asthma; Biomarkers; Cell Adhesion Molecules; Eosinophils; Female; Fluticasone; Glucocorticoids; Humans; Inflammation; Male; Middle Aged; Respiratory Function Tests; Sputum; Statistics as Topic; Tomography, X-Ray Computed; Treatment Outcome

The dose-response relationship between two dose levels of fluticasone/formoterol (flutiform(®), 100/10 μg and 500/20 μg) was evaluated in asthmatic patients. Non-invasive inflammatory markers were used including adenosine monophosphate (AMP) challenge (primary endpoint), and sputum eosinophils and fractional exhaled nitric oxide (FeNO) (secondary endpoints).. Patients aged ≥18 years with forced expiratory volume in 1 s (FEV1) ≥60% predicted and who required a dose of <60 mg AMP to elicit a 20% drop in FEV1 (AMP PD20) were randomised in this incomplete block, crossover study to receive 2 of 3 treatments b.i.d.: fluticasone/formoterol 500/20 μg (high dose), 100/10 μg (low dose) or placebo, during 2 periods of 28 ± 3 days each, separated by 2-3 weeks. AMP challenges were performed pre-dose and 12 h after last dose at the end of each treatment period. A series of post hoc analyses were performed only in patients allocated to both fluticasone/formoterol doses, who completed the study and had evaluable AMP PD20 data for both treatments ("fluticasone/formoterol subgroup"). Changes in AMP PD20 FEV1, percentage sputum eosinophils and FeNO levels (Day 1 vs Day 28) between treatments were compared by an analysis of covariance (ANCOVA).. Sixty-two patients were randomised and 46 completed the study. Fifteen patients received both high- and low-dose fluticasone/formoterol (post hoc subgroup). The difference in AMP PD20 for the overall population was not statistically significant between high- and low-dose fluticasone/formoterol (LS mean fold difference: 1.3; p = 0.489), although both dose levels were superior to placebo: high-dose vs placebo LS mean fold difference: 4.4, p < 0.001; low-dose vs placebo LS mean fold difference: 3.5, p < 0.001. In the post hoc subgroup, the difference in AMP PD20 between the doses was statistically significant in favour of the high-dose (LS mean fold difference: 2.4, p = 0.012). Other inflammatory parameters (sputum eosinophil counts and FeNO) showed small differences and statistically non-significant changes between high- and low-dose fluticasone/formoterol.. A significant dose-response was found between low- and high-dose fluticasone/formoterol in the post hoc subgroup (patients who received both doses), but not in the overall population, with the higher dose demonstrating a greater reduction in airway responsiveness to AMP.

Topics: Adenosine Monophosphate; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Eosinophils; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Nitric Oxide; Sputum

The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate.. In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of life-threatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone-salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation.. Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone-salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthma-related event in the fluticasone-salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P=0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthma-related intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone-salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone-salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001).. Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone-salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group. (AUSTRI ClinicalTrials.gov number, NCT01475721.).

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Intention to Treat Analysis; Male; Middle Aged; Proportional Hazards Models; Severity of Illness Index

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Combinations; Fluticasone; Humans; Salmeterol Xinafoate; Treatment Outcome; Young Adult

Inhaled corticosteroids (ICS) are effective maintenance treatments for childhood asthma; however, many children remain uncontrolled. Vilanterol (VI) is an inhaled long-acting beta-2 agonist which, in combination with the ICS fluticasone furoate, is being explored as a once-daily treatment for asthma in children. We evaluated the dose-response, efficacy, and safety of once-daily VI (6.25 μg, 12.5 μg and 25 μg) administered in the evening over 4 weeks, on background fluticasone propionate (FP) in children with asthma inadequately controlled on ICS.. This was a Phase IIb, multicentre, randomised, double-blind, parallel-group, placebo-controlled study in children ages 5-11 years with persistent asthma on ICS and as-needed short-acting beta-agonist. The study comprised a 4-week run-in, 4-week treatment period, and 1-week follow-up. From study start, children replaced their current ICS with open-label FP 100 μg twice daily. Children were randomised to receive placebo, VI 6.25 μg, VI 12.5 μg or VI 25 μg once daily. Primary endpoint was treatment difference between VI 25 and placebo groups in mean change from baseline in evening peak expiratory flow averaged over the 4-week treatment. Secondary endpoints included change from baseline in trough forced expiratory volume in one second (FEV1) at Week 4 and change from baseline in percentage of rescue-free and symptom-free 24-h periods. Safety assessments included incidence of adverse events (AEs) and asthma exacerbations.. In total, 456 children comprised the intention-to-treat population. The adjusted treatment difference between VI 25 and placebo groups for the primary endpoint was not statistically significant (p = 0.227) so no statistical inference was made for other VI dose comparisons or other endpoints. No difference in change from baseline in trough FEV1 was observed for any VI treatments versus placebo; however, VI 25 resulted in an additional 0.6 rescue-free days and 0.7 symptom-free days per week versus placebo. The incidence of AEs was slightly higher in the VI groups (28-33 %) versus placebo (22 %). Nine children experienced asthma exacerbations during the treatment period.. VI plus FP did not result in significant improvements in lung function versus placebo plus FP, but was well tolerated at all doses assessed.. NCT01573767 (ClinicalTrials.gov).

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Benzyl Alcohols; Bronchodilator Agents; Child; Child, Preschool; Chlorobenzenes; Combined Modality Therapy; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Placebo Effect; Treatment Outcome

Long-acting beta agonists (LABAs) are effective for controlling asthma, however questions about their safety have led to concerns over use. Genetic polymorphisms at the 16 amino acid position of the beta-2 adrenergic receptor gene (B2AR) may be associated with increased risk.. A randomized, double blind study was conducted in patients with moderate to severe asthma being treated with combined inhaled corticosteroids/LABA (ICS/LABA), comparing the effect of LABA continuation versus withdrawal on asthma outcomes among patients stratified by B2AR genotype (Arg/Arg vs. Gly/Gly at the 16th amino acid position).. 67 participants (31 Arg/Arg, 36 Gly/Gly) were randomized to receive fluticasone alone (F) or continue combined fluticasone/salmeterol (F/S) after a run-in period on F/S. Among Gly/Gly subjects, those in the F/S treatment group showed improvement in AM PEFR (+ 8.4 L/s) whereas those receiving F alone experienced a reduction in AM PEFR over the study period (-14.4 L/s), (p = 0.06). There was no significant difference in morning peak expiratory flow rate (AM PEFR) in Arg/Arg participants randomized to receive F/S (-15.7L) vs F alone (-5.6 L/s) (p = 0.61). There was no significant difference in exacerbations in the Arg/Arg subjects treated with F/S compared with those treated with F (p = 0.65).. Withdrawal of LABA therapy in asthmatics with the Arg/Arg genotype at the 16th amino acid position of B2AR did not lead to significant improvement in AM PEFR. LABA withdrawal in the Gly/Gly genotype however led to a borderline significant decline in AM PEFR.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Alleles; Anti-Asthmatic Agents; Arginine; Asthma; Double-Blind Method; Female; Fluticasone; Glycine; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Receptors, Adrenergic, beta-2; Salmeterol Xinafoate; Treatment Outcome

Several guidelines, including the Japanese Pediatric Guideline for the Treatment and Management of Asthma (JPGL), recommend salmeterol/fluticasone combination therapy (SFC) as step 3 to 4 treatment for moderate to severe asthma. However, the optimal step-down approach to SFC remains unclear. In the current study, we examined step-down approaches in asthmatic children whose symptoms had been stabilized by SFC 100/200 μg/day.. This randomized, multicenter, open-label, parallel-group study was conducted over 12 weeks. For step-down therapy, subjects aged 5-15 years were randomly assigned to an SFC group (25/50 μg b.i.d.) or an FP group (100 μg b.i.d.), and treated for 12 weeks. Childhood Asthma Control Test (C-ACT) scores, lung function, and exhaled nitric oxide (FeNO) levels were monitored.. Of 131 enrolled subjects, 128 completed the study and were included in the analysis. Decreases in % peak expiratory flow rate and % forced expiratory flow at 50% of vital capacity (V50) were observed in the FP group at each time point. There was a significant difference between the two groups for the change in %V50 from its previous value at each time point. There were no significant changes in FeNO levels (range 15-20 ppb) or C-ACT scores (∼26 points) within or between groups.. A high level of asthma control was maintained with both approaches. The use of SFC step-down resulted in somewhat better respiratory function, with no worsening of airway inflammation. However, halving the dose of SFC and switching to FP alone are both optimal step-down approaches.

Topics: Adolescent; Asthma; Child; Child, Preschool; Drug Administration Schedule; Drug Combinations; Exhalation; Female; Fluticasone; Humans; Male; Nitric Oxide; Respiratory Function Tests; Salmeterol Xinafoate; Treatment Outcome

The present study was conducted to assess the efficacy, safety and tolerability of fluticasone propionate/formoterol fumarate combination therapy (FP/FORM; Flutiform®) compared with fluticasone propionate/salmeterol xinafoate (FP/SAL; Seretide® Evohaler®) in children with asthma.. This was an open-label, randomized, controlled, phase III trial and extension. Patients aged 4-12 years with reversible asthma [% predicted forced expiratory volume in 1 second (FEV1) 60-100%; documented reversibility of ⩾15% in FEV1] were randomized to receive FP/FORM (100/10 µg b.i.d.) or FP/SAL (100/50 µg b.i.d.) for 12 weeks. Eligible patients completing the 12-week core phase entered a 24-week extension phase with FP/FORM (100/10 µg b.i.d.). The primary efficacy endpoint was the change in predose FEV1 from day 0 to day 84. Secondary efficacy endpoints included change in predose to 2-hours postdose FEV1 from day 0 to day 84, peak expiratory flow rate (PEFR), patient-reported outcomes, rescue-medication use and asthma exacerbations.. In total, 211 patients were randomized and 210 completed the core phase; of these patients, 208 entered and 205 completed the extension phase of the study. Predose FEV1 increased from day 0 to day 84 [FP/FORM, 182 ml; 95% confidence interval (CI), 127, 236; FP/SAL, 212 ml, 95% CI, 160, 265] and FP/FORM was noninferior to FP/SAL: least squares (LS) mean treatment difference: -0.031 (95% CI, -0.093, 0.031; p = 0.026). Secondary efficacy analyses indicated similar efficacy with both therapies. There were no notable differences observed in the safety and tolerability profile between treatments. No safety concerns were identified with long-term FP/FORM therapy, and there was no evidence of an effect of FP/FORM on plasma cortisol.. FP/FORM improved lung function and measures of asthma control with comparable efficacy to FP/SAL, and demonstrated a favourable safety and tolerability profile in children aged 4-12 years.

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Drug Combinations; Ethanolamines; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Peak Expiratory Flow Rate; Respiratory Function Tests; Treatment Outcome

The prognostic value of asthma biomarkers in routine clinical practice is not fully understood. ARIETTA (NCT02537691) is an ongoing, prospective, longitudinal, international, multicentre real-world study designed to assess the relationship between asthma biomarkers and disease-related health outcomes. The trial aims to enrol and follow for 52 weeks approximately 1200 severe asthma patients from approximately 160 sites in more than 20 countries. Severe asthmatics, treated with daily inhaled corticosteroid (≥500 μg of fluticasone propionate or equivalent) and at least 1 second controller medication are to be included. In this real-world study, patients will be treated according to the investigator's routine clinical practices and no treatment regimen will be implemented as part of the trial. At baseline and again at 26 and 52 weeks, FEV1, FeNO, serum periostin, blood eosinophil count and serum IgE will be measured. Asthma-related symptom and quality of life questionnaires will be administered at the visits and during telephone interviews at Weeks 13 and 39. Data about medication use, asthma exacerbation data, asthma-related healthcare utilization and events raising safety concerns will also be collected. This study design, unique in both its scope and scale, will address fundamental unanswered questions regarding asthma biomarkers and their interrelationship, as well as predict deviations in the course of asthma in a real-world setting.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Asthma; Biomarkers; Cell Adhesion Molecules; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Humans; Immunoglobulin E; Male; Nitric Oxide; Predictive Value of Tests; Prognosis; Prospective Studies; Quality of Life; Severity of Illness Index

Inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) association offers a better asthma control than a higher steroid dose with short-acting beta-agonists as needed. In this study, we evaluated the effect of the association on bronchial hyperreactivity (BHR) and peak expiratory flow (PEF) variability, as such parameters are positively correlated with increased asthma morbidity and exacerbations. Thirty-six adult patients with mild persistent asthma were enrolled. After a 7-day run-in, they were randomly assigned to three therapy regimens for 6 weeks: Group 1, fluticasone 125 μg + formoterol 5 μg in the same device; Group 2, fluticasone 125 μg + formoterol 12 μg as needed; Group 3, fluticasone 250 μg + formoterol 12 μg as needed. We evaluated changes induced in weekly PEF variability (measured during the entire study and 4 weeks of follow-up) and pre- and post-study PD20 methacholine (MCH). Weekly PEF variability decreased in all groups during treatment with the greatest reduction in Group 1, followed by Group 3, and finally Group 2. During the follow-up, no significant changes were detected in Group 1, whereas a trend towards an increased variability was found in Groups 2 and 3. Post-treatment PD20 MCH was significantly higher versus the pre-treatment. The increase observed in Group 1 was significantly higher compared to Groups 2 and 3 and that observed in Group 3 in respect to Group 2. The study proves that both BHR and PEF variability are influenced by ICS. This effect was greater with fluticasone/formoterol association compared to fluticasone alone with formoterol as needed even at higher steroid dose.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Bronchoconstrictor Agents; Bronchodilator Agents; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Methacholine Chloride; Peak Expiratory Flow Rate

Topics: Allergens; Asthma; Biomarkers; C-Reactive Protein; Child; Dipeptidyl Peptidase 4; Drug Therapy, Combination; Eosinophils; Female; Fluticasone; Humans; Ki-1 Antigen; Lymphocyte Activation; Male; Respiratory Sounds; Salmeterol Xinafoate; Spirometry; Th1 Cells; Th2 Cells; Treatment Outcome

Long-acting beta-agonists (LABAs) have been shown to increase the risk of asthma-related death among adults and the risk of asthma-related hospitalization among children. It is unknown whether the concomitant use of inhaled glucocorticoids with LABAs mitigates those risks. This trial prospectively evaluated the safety of the LABA salmeterol, added to fluticasone propionate, in a fixed-dose combination in children.. We randomly assigned, in a 1:1 ratio, children 4 to 11 years of age who required daily asthma medications and had a history of asthma exacerbations in the previous year to receive fluticasone propionate plus salmeterol or fluticasone alone for 26 weeks. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization), as assessed in a time-to-event analysis. The statistical design specified that noninferiority would be shown if the upper boundary of the 95% confidence interval of the hazard ratio for the primary safety end point was less than 2.675. The main efficacy end point was the first severe asthma exacerbation that led to treatment with systemic glucocorticoids, as assessed in a time-to-event analysis.. Among the 6208 patients, 27 patients in the fluticasone-salmeterol group and 21 in the fluticasone-alone group had a serious asthma-related event (all were hospitalizations); the hazard ratio with fluticasone-salmeterol versus fluticasone alone was 1.28 (95% confidence interval [CI], 0.73 to 2.27), which showed the noninferiority of fluticasone-salmeterol (P=0.006). A total of 265 patients (8.5%) in the fluticasone-salmeterol group and 309 (10.0%) in the fluticasone-alone group had a severe asthma exacerbation (hazard ratio, 0.86; 95% CI, 0.73 to 1.01).. In this trial involving children with asthma, salmeterol in a fixed-dose combination with fluticasone was associated with the risk of a serious asthma-related event that was similar to the risk with fluticasone alone. (Funded by GlaxoSmithKline; VESTRI ClinicalTrials.gov number, NCT01462344 .).

Topics: Administration, Inhalation; Adrenergic beta-1 Receptor Agonists; Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Child; Child, Preschool; Delayed-Action Preparations; Double-Blind Method; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Male; Metered Dose Inhalers; Proportional Hazards Models

This phase III trial had two treatment periods (P): P1, patients with well-controlled asthma on FP/SAL 250/50 μg BD equivalent stepped across to once daily (OD) FF/VI 100/25 μg (open-label, eight weeks); P2, patients remaining 'well controlled' after P1 stepped down to FF 100 μg OD/FP 100 μg BD/FP 250 μg BD (randomized 1:1:1, double-blind, 12 weeks). Co-primary P2 endpoints: percentage of patients with well-controlled asthma; time to withdrawal due to poorly controlled asthma requiring step-up therapy. Adverse events (AEs) were monitored.. At the end of P1 (n = 430), 373 (90.5%; 95% confidence interval 87.29-93.18) patients' asthma remained well controlled with FF/VI; in P2 (n = 371), control was maintained in 89.5% (FF 100 μg)/79.5% (FP 100 μg)/83.8% (FP 250 μg) of patients. In P2, 4.9-7.3% of patients were withdrawn due to worsening asthma (time-to-withdrawal cumulative incidence curves were comparable). AEs were reported by 37% of patients during P1; and by 36% (FF 100 μg)/48% (FP 100 μg)/49% (FP 250 μg) of patients in P2.. For patients with well-controlled asthma on mid dose ICS/LABA (equivalent to FP/SAL 250/50 μg BD), control can be maintained when they are stepped across to FF/VI 100/25 μg OD. FF 100 μg OD is an effective step-down therapy from FF/VI 100/25 μg OD with similar efficacy to FP 100 μg BD and FP 250 μg BD.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Androstadienes; Asthma; Benzyl Alcohols; Chlorobenzenes; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Japan; Male; Middle Aged; Peak Expiratory Flow Rate; Prevalence; Smoking; Treatment Outcome

To evaluate and contrast the therapeutic effect and safety of fluticasone aerosol combined with theophylline tablets in patients with moderate to severe asthma, compared with salmeterol/fluticasone propionate aerosol.. After a screening period, patients meeting the inclusion criteria were randomly assigned to the experiment group (fluticasone aerosol combined with theophylline tablets) or the control group (salmeterol/fluticasone aerosol combined with placebo tablets) for 12 weeks of treatment. The main outcome measurements were forced expiratory volume in 1 second and fractional concentration of exhaled nitric oxide value, whereas the secondary measures were forced vital capacity, peak expiratory flow value, and Asthma Control Test/Asthma Quality of Life Questionnaire score.. Forty-four cases completed the course, with 23 cases in the experiment group and 21 cases in the control group. The forced expiratory volume in 1 second values of both groups were significantly improved from before (P < 0.05). The fractional concentration of exhaled nitric oxide values of both groups were significantly decreased from before (P < 0.05). The secondary outcome measurements after treatment achieved obvious improvement from baseline (P < 0.05) in both. There was no significant difference between the 2 groups in all measurements. In addition, the blood biochemistry results, ECG results, and vital signs of both groups had no significant abnormality.. There was no significant difference in therapeutic effect and safety between the 2 groups in treating patients with moderate to severe persistent asthma, which suggests that fluticasone aerosol combined with theophylline tablets is worth considering for use in primary hospitals or for low-income populations.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aerosols; Aged; Albuterol; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Quality of Life; Theophylline; Treatment Outcome

While several randomized control trials (RCTs) have evaluated the use of fractional exhaled nitric oxide (FeNO) to improve asthma outcomes, none used FeNO cut-offs adjusted for atopy, a determinant of FeNO levels. In a dual center RCT, we assessed whether a treatment strategy based on FeNO levels, adjusted for atopy, reduces asthma exacerbations compared with the symptoms-based management (controls). Children with asthma from hospital clinics of two hospitals were randomly allocated to receive an a-priori determined treatment hierarchy based on symptoms or FeNO levels. There was a 2-week run-in period and they were then reviewed 10 times over 12-months. The primary outcome was the number of children with exacerbations over 12-months. Sixty-three children were randomized (FeNO = 31, controls = 32); 55 (86%) completed the study. Although we did achieve our planned sample size, significantly fewer children in the FeNO group (6 of 27) had an asthma exacerbation compared to controls (15 of 28), P = 0.021; number to treat for benefit = 4 (95% CI 3-24). There was no difference between groups for any secondary outcomes (quality of life, symptoms, FEV1 ). The final daily inhaled corticosteroids (ICS) dose was significantly (P = 0.037) higher in the FeNO group (median 400 µg, IQR 250-600) compared to the controls (200, IQR100-400). Taking atopy into account when using FeNO to tailor asthma medications is likely beneficial in reducing the number of children with severe exacerbations at the expense of increased ICS use. However, the strategy is unlikely beneficial for improving asthma control. A larger study is required to confirm or refute our findings.

Topics: Adolescent; Asthma; Breath Tests; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Exhalation; Female; Fluticasone; Humans; Male; Nitric Oxide; Quality of Life; Treatment Outcome

Fluticasone propionate and formoterol fumarate have been combined in a single inhaler (fluticasone/formoterol; flutiform(®)) for the maintenance treatment of asthma. This pooled analysis assessed the efficacy of fluticasone/formoterol versus fluticasone in patients who previously received inhaled corticosteroids.. Data were pooled from five randomised studies in patients with asthma (aged ≥12 years) treated for 8 or 12 weeks with fluticasone/formoterol (100/10, 250/10 or 500/20 μg b.i.d.; n = 528 delivered via pMDI) or fluticasone alone (100, 250 or 500 μg b.i.d.; n = 527).. Fluticasone/formoterol provided significantly greater increases than fluticasone alone in mean morning forced expiratory volume in 1 second (FEV1) from pre-dose at baseline to 2 hours post-dose at study end (least-squares mean [LSM] treatment difference: 0.146L; p < 0.001) and in pre-dose FEV1 from baseline to study end (LSM treatment difference: 0.048 L; p = 0.043). Compared with fluticasone, fluticasone/formoterol provided greater increases in the percentage of asthma control days (no symptoms, no rescue medication use and no sleep disturbance due to asthma) from baseline to study end (LSM treatment difference: 8.6%; p < 0.001), and was associated with a lower annualised rate of exacerbations (rate ratio: 0.71; p = 0.014).. In summary, fluticasone/formoterol provides clinically significant improvements in lung function and asthma control measures, with a lower incidence of exacerbations than fluticasone alone.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Treatment Outcome; Young Adult

Phase III/IV clinical trials are expensive and time consuming and often suffer from poor enrollment and retention rates. Pediatric trials are particularly difficult because scheduling around the parent, participant and potentially other sibling schedules can be burdensome. We are evaluating using the internet and mobile devices to conduct the consent process and study visits in a streamlined pediatric asthma trial. Our hypothesis is that these study processes will be non-inferior and will be less expensive compared to a traditional pediatric asthma trial.. Parents and participants, aged 12 through 17 years, complete the informed consent process by viewing a multi-media website containing a consent video and study material in the streamlined trial. Participants are provided an iPad with WiFi and EasyOne spirometer for use during FaceTime visits and online twice daily symptom reporting during an 8-week run-in followed by a 12-week study period. Outcomes are compared with participants completing a similarly designed traditional trial comparing the same treatments within the same pediatric health-system. After 8 weeks of open-label Advair 250/50 twice daily, participants in both trial types are randomized to Advair 250/50, Flovent 250, or Advair 100/50 given 1 inhalation twice daily. Study staff track time spent to determine study costs.. Participants have been enrolled in the streamlined and traditional trials and recruitment is ongoing.. This project will provide important information on both clinical and economic outcomes for a novel method of conducting clinical trials. The results will be broadly applicable to trials of other diseases.

Topics: Adolescent; Asthma; Bronchodilator Agents; Child; Computers, Handheld; Data Collection; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Informed Consent; Internet; Male; Multimedia; Research Design; Spirometry

The prostaglandin D2 (PGD2) receptor, CRTH2, plays a role in allergic airway inflammation. The efficacy of BI 671800, a CRTH2 antagonist, was assessed in 2 separate trials in patients with asthma, in either the absence or the presence of inhaled corticosteroid (ICS) therapy. In this study, BI 671800 (50, 200 or 400 mg) and fluticasone propionate (220 μg) all given twice daily (bid) were compared with bid placebo in symptomatic controller-naïve adults with asthma (Trial 1), and BI 671800 400 mg bid compared with montelukast 10 mg once daily (qd), and matching placebo bid, in patients with asthma receiving inhaled fluticasone (88 μg bid) (Trial 2). The primary endpoint in both trials was change from baseline in trough forced expiratory volume in 1 s (FEV1) percent predicted. After 6 weeks' treatment, adjusted mean treatment differences (SE) for the primary endpoint compared with placebo in Trial 1 were 3.08% (1.65%), 3.59% (1.60%) and 3.98% (1.64%) for BI 671800 50, 200 and 400 mg bid, respectively, and 8.62% (1.68%) for fluticasone 220 μg bid (p = 0.0311, p = 0.0126, p = 0.0078 and p < 0.0001, respectively). In Trial 2, adjusted mean FEV1 (SE) treatment differences compared with placebo were 3.87% (1.49%) for BI 671800 400 mg bid and 2.37% (1.57%) for montelukast (p = 0.0050 and p = 0.0657, respectively). These findings suggest that BI 671800 is associated with a small improvement in FEV1 in symptomatic controller-naïve asthma patients, and in patients on ICS.

Topics: Administration, Inhalation; Adult; Anti-Asthmatic Agents; Asthma; Benzamides; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Pyrimidines; Receptors, Immunologic; Receptors, Prostaglandin; Treatment Outcome; Young Adult

Genetic polymorphisms may be responsible for the wide variation in response to inhaled corticosteroids in asthmatic patients. We had previously reported that one polymorphism rs7772821, located on the 3'-UTR of trace amine-associated receptor 6 (TAAR6), is significantly associated with percentile changes in the forced expiratory volume in 1 s (%ΔFEV1) after inhaled corticosteroid treatment in asthmatics using a genome-wide association study. The aim of the present study was to validate the association between 15 single-nucleotide polymorphisms (SNPs) on the TAAR6 and airway responsiveness to inhaled corticosteroids in the asthmatics.. The %ΔFEV1 induced by 4 weeks' treatment with inhaled fluticasone propionate (1000 μg daily) was measured in 246 asthmatics. The 15 SNPs of TAAR6 were genotyped using a TaqMan assay. An association analysis between %ΔFEV1 and TAAR6 polymorphisms was carried out using a linear regression model controlling for age, sex, smoking status, presence of atopy, and baseline FEV1 as covariates.. Among the 15 SNPs and seven haplotypes of TAAR6, rs7772821 (T>G) on the 3'-UTR showed the strongest correlation with inhaled corticosteroid-induced %ΔFEV1 (Pcorr=0.002 in the codominant model, Pcorr=0.03 in the dominant model, Pcorr=0.01 in the recessive model). The %ΔFEV1 of the rs7772821T>G minor homozygotes (60.77%) was higher than that of patients harboring either the rs7772821 T/G or T/T genotypes (21.32 and 31.60%, respectively).. The TAAR6 rs7772821 polymorphism may be one of the important genetic factors for predicting the response to treatment with inhaled corticosteroids in asthmatics.

Topics: 3' Untranslated Regions; Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Inflammatory Agents; Asthma; Cell Cycle Proteins; Female; Fluticasone; Forced Expiratory Volume; Gene Frequency; Genetic Association Studies; Haplotypes; Humans; Male; Middle Aged; Nuclear Proteins; Polymorphism, Single Nucleotide; Prospective Studies; Receptors, G-Protein-Coupled; Young Adult

In this study, we compared the clinical and immunological efficacy of nebulized corticosteroid (CS) to systemic route during treatment of moderate asthma attack in children.. In this randomized, placebo-controlled, double-blind, double-dummy, prospective study, 81 children aged 12 months to 16 years experiencing asthma attack randomized into two treatment groups to receive, either; nebulized fluticasone propionate (n = 39, 2000 mcg/day) or oral methylprednisolone (n = 41, 1 mg/kg/day). Pulmonary index scores (PIS) were assessed at admission and at 1st, 4th, 8th, 12th, 24th, 48th hours, as well as, on day 7 and peak expiratory flow (PEF) at baseline and at the 7th day. Daily symptom and medication scores were recorded for all subjects. Immunological studies included phytohemagglutinin induced peripheral blood mononuclear cells culture supernatant for cytokine responses and CD4(+) CD25(+) FOXP3(+) T regulatory cell (T reg) percentage at baseline and day 7.. The changes in PIS and PEF were similar in both treatment groups, with a significant improvement in both values at the 7th day, when compared to baseline. In both groups, significant reductions in symptom and medication scores were observed during the treatment period with no significant difference between the groups. At day 7 of intervention, phytohemagglutinin induced IL-4 level was significantly decreased only in the nebulized group compared to baseline (p = 0.01). Evaluation of cytokine responses by means of fold increase (stimulated (S)/unstimulated (US) ratio) revealed a significant reduction in IL-4, IL-5 and IL-17 only in nebulized group (p = 0.01, 0.01, 0.02; respectively). The fold increase value of IL-5 was significantly lower at 7th day in nebulized group when compared to systemic one (p = 0.02). At 7th day, although in both treatment groups the percentage of T reg cells was suppressed, it remained significantly higher in the nebule one when compared to systemic route (p = 0.04).. In the management of moderate acute asthma attack, nebulized CS (2000 mcg daily) was found to be as effective as systemic route with regard to clinical improvement. In addition, immunological parameters were more in favor of nebulized route which may imply a salutary effect of local CS usage.

Topics: Adolescent; Asthma; Bronchodilator Agents; Child; Child, Preschool; Cytokines; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Infant; Male; Methylprednisolone; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Prospective Studies; T-Lymphocytes, Regulatory

Interleukin 13 is a central mediator of asthma. Tralokinumab is a human interleukin-13 neutralising monoclonal antibody. We aimed to assess the efficacy and safety of two dosing regimens of tralokinumab in patients with severe uncontrolled asthma.. We did a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 2b study at 98 sites in North America, South America, Europe, and Asia. Patients aged 18-75 years with severe asthma and two to six exacerbations in the previous year were randomly assigned (1:1), via an interactive voice-response or web-response system, to one of two dosing regimen groups (every 2 weeks, or every 2 weeks for 12 weeks then every 4 weeks) and further randomised (2:1), via computer-generated permuted-block randomisation (block size of six), to receive tralokinumab 300 mg or placebo for 1 year. All participants received high-dose fluticasone and salmeterol and continued other pre-study controller drugs. Treatment was administered by an unmasked study investigator not involved in the management of patients; all other study site personnel, patients, the study funder, and data analysts were masked to treatment allocation. The primary endpoint was the annual asthma exacerbation rate at week 52 in the intention-to-treat population. Key secondary endpoints included prebronchodilator forced expiratory volume in 1 s (FEV1), Asthma Control Questionnaire-6 (ACQ-6), and Asthma Quality of Life Questionnaire-Standardised Version (AQLQ[S]). This trial is registered with ClinicalTrials.gov, number NCT01402986.. Between Oct 4, 2011, and Feb 22, 2014, we randomly assigned 452 patients to receive placebo (n=151) or tralokinumab every 2 weeks (n=150) or every 4 weeks (n=151), of whom 383 (85%) completed the treatment period up to week 52. The annual asthma exacerbation rate at week 52 was similar between patients receiving tralokinumab every 2 weeks (0.91 per patient per year [95% CI 0.76-1.08]) and every 4 weeks (0.97 [0.81-1.14]), and those receiving placebo (0.90 [0.75-1.08]). At week 52, percentage changes in annual asthma exacerbation rate were not significant with tralokinumab every 2 weeks or every 4 weeks versus placebo (6% [95% CI -31 to 33; p=0.709] and -2% [-46 to 29; p=0.904], respectively), with positive changes showing a decrease in exacerbation rate and negative changes showing an increase. Prebronchodilator FEV1 was significantly increased compared with placebo for tralokinumab every 2 weeks (change from baseline 7.3% [95% CI 2.6-12.0]; p=0.003), but not every 4 weeks (1.8% [-2.9 to 6.6]; p=0.448); however, we did not identify significant changes in the other key secondary endpoints. In a post-hoc subgroup analysis of patients not on long-term oral corticosteroids and with baseline FEV1 reversibility of 12% or greater, we noted a non-significant improvement in asthma exacerbation rate (44% [95% CI -22 to 74]; p=0.147) and significant improvements in key secondary endpoints (FEV1 12.2% [1.7-22.7]; p=0.022; ACQ-6 -0.55 [-1.07 to -0.04]; p=0.036; and AQLQ[S] 0.70 [0.12-1.28]; p=0.019) in patients given tralokinumab every 2 weeks (n=33) compared with placebo (n=48). In patients in this subgroup who also had baseline serum dipeptidyl peptidase-4 (DPP-4) higher than the population baseline median, we noted additional improvements in prebronchodilator FEV1, ACQ-6, and AQLQ(S), and, in those with periostin concentrations higher than the median, we noted improvements in asthma exacerbation rate, prebronchodilator FEV1, and ACQ-6. The incidence of treatment-emergent adverse events was similar between the tralokinumab and placebo groups. Treatment-emergent serious adverse events regarded as related to the study drug were pneumonia (one [1%] patient in the placebo group), pneumococcal pneumonia (one [1%] in the tralokinumab every 2 weeks group), angioedema (one [1%] in the placebo group), and worsening asthma (one [1%] in the tralokinumab every 2 weeks group and two [1%] in the tralokinumab every 4 weeks group).. In this phase 2b study, both tralokinumab regimens had an acceptable safety and tolerability profile but did not significantly reduce asthma exacerbation rates in patients with severe uncontrolled asthma. Improvement in FEV1 with tralokinumab given every 2 weeks and results of post-hoc subgroup analyses suggested a possible treatment effect in a defined population of patients with severe uncontrolled asthma. This effect is being further investigated in ongoing phase 3 trials, along with the potential utility of DPP-4 and periostin as biomarkers of interleukin-13 pathway activation.. MedImmune.

Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Antibodies, Monoclonal; Asthma; Bronchodilator Agents; Disease Progression; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Quality of Life; Salmeterol Xinafoate; Surveys and Questionnaires; Treatment Outcome; Young Adult

It is thought that asthmatics who smoke cigarettes respond less well to inhaled corticosteroid (ICS) therapy than asthmatics who do not smoke.. To evaluate the effects of smoking on allergen-induced airway responses in asthmatics treated with ICS.. Randomized, double-blind, crossover study evaluating twice daily fluticasone propionate (FP) 100 μg, FP 500 μg and placebo, for 7 days, on allergen-induced asthmatic responses in 18 non-smoking and 17 smoking atopic asthmatics (NCT01400906). At 1 h post-morning dose on Day 6, forced expiratory volume in 1 sec (FEV1 ) was measured up to 10 h post-challenge. Exhaled nitric oxide (eNO), induced sputum cell counts, and responsiveness to methacholine were assessed the following day.. The late asthmatic response (LAR) was suppressed by FP in smokers and non-smokers; with placebo, the LAR was also attenuated in smokers versus non-smokers (adjusted mean minimum change in FEV1 (L) over 4-10 h [95% CI] in non-smokers: placebo -1.01 [1.31, 0.70], FP 100 μg -0.38 [0.54, 0.22], FP 500 μg -0.35 [0.54-0.22]; and in smokers: placebo -0.63 [0.84, 0.43]; FP 100 μg -0.44 [0.65, 0.23]; FP 500 μg -0.46 [0.59-0.32]). The Early AR was suppressed by FP treatment in non-smokers, but was not impacted in smokers. The reduction in methacholine hyperresponsiveness after FP was greater in non-smokers (1.5- and twofold doubling dose difference from placebo after FP 100 μg and FP 500 μg) than smokers (1.0 and 1.3 difference, respectively). Allergen-induced increases in eNO and sputum eosinophils were lower in smokers than non-smokers and were suppressed in both groups by FP.. Allergen-induced LARs were of a similar amplitude in both smoking and non-smoking atopic asthmatics at the end of ICS treatment, but attenuation of the LAR in smokers was only partly associated with ICS treatment. The marked attenuation of the LAR observed in smokers in the absence of ICS treatment is a novel observation.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Allergens; Asthma; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Smoking

Despite extensive use of inhaled corticosteroid/long-acting β2-agonist combinations in asthma, limited data evaluating dose-response for this combination class are available. The benefits of dose escalation and nature of patient subgroups likely to benefit are thus ill-defined.. In this randomised, double-blind, 8-week study the effects of two dose levels (100/10 and 500/20 μg b.i.d.) of a fixed combination of fluticasone/formoterol (flutiform(®)) were compared in 309 patients. Treatment effects upon spirometric and symptom-based endpoints were examined in the overall population and in two subgroups defined a priori by % predicted FEV1 at baseline (≥40-≤60% ["severe" airways obstruction] and >60-≤80% ["moderate" airways obstruction]).. No dose-response was evident for spirometric outcomes (FEV1, FEV1 AUC0-12, PEFR) either overall or in either subgroup. At variance with the spirometric data, statistically significant dose-dependent differences were seen for nocturnal outcomes and consistent numerical differences were found across multiple symptom-based outcomes (symptom scores, sleep scores, rescue medication use, asthma control days, AQLQ scores, exacerbations); greater effects were noted with the higher dose of fluticasone/formoterol. Between-group differences for the overall population were driven by treatment effect differences in the "severe" subgroup.. In this exploratory comparison a high dose of fluticasone/formoterol in asthmatic patients appears to provide additional improvement in symptom-based rather than spirometric outcomes. Additional benefits from high versus low dose treatment are most likely in patients with severe airway obstruction, although the doses at which ceiling effects are attained may vary between individuals.. ClinicalTrials.gov identifier: NCT00734318; EudraCT number: 2007-001633-34.

Topics: Adult; Aged; Anti-Asthmatic Agents; Asthma; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Endpoint Determination; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Respiratory Function Tests; Spirometry; Treatment Outcome

Regular treatment with inhaled corticosteroids (ICS) is known to reduce airway hyperresponsiveness (AHR) to adenosine 5'-monophosphate (AMP) in asthma even after a single dose of fluticasone propionate (FP).. To determine whether this rapid protective effect of a single dose of FP is also present in COPD.. 23 mild asthmatic and 24 COPD subjects with documented AHR to both AMP and methacholine took part in a randomized, double-blind, placebo-controlled, crossover study to measure AHR to inhaled AMP and methacholine 2 h after either 1000 μg FP or matched placebo.. In subjects with asthma, 1000 μg FP in a single dose significantly attenuated the constrictor response to AMP, geometric mean (range) PC20AMP values increasing from a 19.2 (1.3-116.3) to 81.5 (9.6-1600.0) (p < 0.001; post-placebo vs post-FP) mg/ml. Change in the airways response to inhaled AMP after FP was well within test variability in patients with COPD, with PC20AMP values 59.6 (11.3-183.9) and 76.3 (21.0-445.3) (p = 0.022; post-placebo vs post-FP) mg/ml. Additionally, FP failed to significantly attenuate the bronchial response to methacholine in both asthma and COPD subjects. A change in doubling dilution, between placebo and following a single dose of FP, in AMP had a better sensitivity and specificity of 95.8% and 65.2%, compared to methacholine of 79.2% and 43.5% respectively in delineating between COPD and asthma.. A single dose of 1000 μg FP rapidly improves AHR to AMP in asthmatics but not in COPD subjects. This may provide a convenient way by which provocation challenge with inhaled AMP may help in discriminating asthma from COPD.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adult; Aged; Androstadienes; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Male; Methacholine Chloride; Middle Aged; Pulmonary Disease, Chronic Obstructive; Sensitivity and Specificity

To examine serum cortisol responses to a simplified low-dose short Synacthen test (LDSST) in children treated with inhaled corticosteroids (ICS) for asthma and to compare these to early morning salivary cortisol (EMSC) and cortisone (EMSCn) levels.. Early morning salivary cortisol and EMSCn samples were collected for three consecutive days. On day three, Synacthen 500 ng/1·73 m(2) was administered intravenously. Samples were collected at 0, 15, 25, 35 min.. A total of 269 subjects (160 M: 109 F), median (range) age 10·0 (5·1-15·2) years were studied. Peak cortisol in the LDSST was <500 nmol/l in 101 subjects (37·5%) and <350 nmol/l in 12 subjects (4·5%). Basal cortisol correlated with peak cortisol: r = 0·55, (95% CI: 0·46, 0·63, P < 0·0001). Time at which peak cortisol concentration was achieved was significantly related to the value of peak cortisol (P < 0·0001), with higher cortisol peaks occurring later in the test and lower cortisol peaks occurring earlier. EMSC and EMSCn had no predictive value for the identification of patients with a peak cortisol <500 nmol/l. EMSCn was superior to EMSC in identifying patients with a peak cortisol <350 nmol/l: a minimum EMSCn cut-off value of 12·5 nmol/l gave a negative predictive value of 99·2% and positive predictive value of 30·1%.. Our data illustrate that basal measures of cortisol are likely to be of value in screening populations for patients at greatest risk of adrenal crisis. EMSCn shows promise as a screening tool for the identification of patients with severe adrenal insufficiency.

Topics: Adolescent; Adrenal Glands; Adrenal Insufficiency; Androstadienes; Asthma; Bronchodilator Agents; Child; Child, Preschool; Circadian Rhythm; Cortisone; Cosyntropin; Dose-Response Relationship, Drug; Fluticasone; Humans; Hydrocortisone; Pituitary-Adrenal Function Tests; Saliva

Predictors of improvement in asthma control and lung function to step 3 therapy in children with persistent asthma have not been identified despite reported heterogeneity in responsiveness.. We sought to evaluate potential predictors of asthma control and lung function responsiveness to step 3 therapy.. A post hoc analysis from the Best Add-On Giving Effective Response (BADGER) study tested the association between baseline biological, asthma control, pulmonary function, and demographic markers and responsiveness to step-up to a higher dose of inhaled corticosteroid (ICS step-up therapy) or addition of leukotriene receptor antagonist (LTRA step-up therapy) or long-acting β₂-agonist (LABA step-up therapy).. In multivariate analyses higher impulse oscillometry reactance area was associated (P = .048) with a differential FEV₁ response favoring LABA over ICS step-up therapy, whereas higher urinary leukotriene E₄ levels were marginally (P = .053) related to a differential FEV₁ response favoring LTRA over LABA step-up therapy. Predictors of differential responses comparing ICS with LTRA step-up therapy were not apparent, probably because of suppression of allergic markers with low-dose ICS treatment. Minimal overlap was seen across FEV₁ and asthma control day predictors, suggesting distinct mechanisms related to lung function and asthma control day responses.. Levels of impulse oscillometry reactance area indicating peripheral airway obstruction and urinary leukotriene E₄ levels indicating cysteinyl leukotriene inflammation can differentiate LABA step-up responses from responses to LTRA or ICS step-up therapy. Further studies with physiologic, genetic, and biological markers related to these phenotypes will be needed to predict individual responses to LABA step-up therapy.

Topics: Acetates; Adolescent; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Biomarkers; Bronchodilator Agents; Child; Cross-Over Studies; Cyclopropanes; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Humans; Leukocyte Count; Leukotriene Antagonists; Leukotriene E4; Male; Quinolines; Salmeterol Xinafoate; Sulfides; Vital Capacity

Topics: Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptors, Glucocorticoid; White People; Young Adult

Childhood asthma clusters, or subclasses, have been developed by computational methods without evaluation of clinical utility.. To replicate and determine whether childhood asthma clusters previously identified computationally in the Severe Asthma Research Program (SARP) are associated with treatment responses in Childhood Asthma Research and Education (CARE) Network clinical trials.. A cluster assignment model was determined by using SARP participant data. A total of 611 participants 6 to 18 years old from 3 CARE trials were assigned to SARP pediatric clusters. Primary and secondary outcomes were analyzed by cluster in each trial.. CARE participants were assigned to SARP clusters with high accuracy. Baseline characteristics were similar between SARP and CARE children of the same cluster. Treatment response in CARE trials was generally similar across clusters. However, with the caveat of a smaller sample size, children in the early-onset/severe-lung function cluster had best response with fluticasone/salmeterol (64% vs 23% 2.5× fluticasone and 13% fluticasone/montelukast in the Best ADd-on Therapy Giving Effective Responses trial; P = .011) and children in the early-onset/comorbidity cluster had the least clinical efficacy to treatments (eg, -0.076% change in FEV1 in the Characterizing Response to Leukotriene Receptor Antagonist and Inhaled Corticosteroid trial).. In this study, we replicated SARP pediatric asthma clusters by using a separate, large clinical trials network. Early-onset/severe-lung function and early-onset/comorbidity clusters were associated with differential and limited response to therapy, respectively. Further prospective study of therapeutic response by cluster could provide new insights into childhood asthma treatment.

Topics: Acetates; Adolescent; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides

The methacholine challenge test quantifies airway hyper-responsiveness, which is measured by the provocative concentration of methacholine causing a 20% decrease in forced expiration volume in 1 second (PC20). The dose-response effect of inhaled corticosteroids (ICS) on PC20 has been inconsistent and within-patient variability of PC20 is not well established.. To determine the effect of high- vs low-dose ICS on PC20 and within-patient variability in those with repeated measurements of PC20.. A randomized, double-masked, crossover trial was conducted in patients with asthma on controller medications with PC20 of 8 mg/mL or lower (n = 64) to evaluate the effect of high-dose (1,000 μg/d) vs low-dose (250 μg/d) fluticasone for 4 weeks on PC20. In addition, the variability of PC20 was assessed in participants who underwent 2 or 3 PC20 measurements on the same dose of ICS (n = 27) over a 4-week interval.. Because there was a significant period effect, dose comparison of the change in PC20 was assessed in the first treatment period. There was no significant difference in the change in PC20 for high- vs low-dose ICS (39% vs 30% increase, respectively; P = .87). The within- and between-participant variances for log PC20 were 0.84 and 0.96, respectively, with an intra-class correlation of 0.53, and 37% of participants had more than 2 doubling dose changes in PC20 in those with repeated measurements.. The effect of ICS on PC20 is not dose dependent at fluticasone levels of 250 and 1,000 μg/d. Interpersonal variability for PC20 is large. A lack of precise measurements should be taken into account when interpreting any change in PC20.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Asthma; Bronchial Provocation Tests; Child; Cross-Over Studies; Diagnostic Errors; Disease Progression; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; Male; Methacholine Chloride; Middle Aged; Reproducibility of Results; Young Adult

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Drug Delivery Systems; Dry Powder Inhalers; Female; Fluticasone; Humans; Male; Metered Dose Inhalers

Topics: Acetates; Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Black or African American; Child; Cross-Over Studies; Cyclopropanes; Drug Combinations; Drug Monitoring; Eczema; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Hispanic or Latino; Humans; Male; Quinolines; Sulfides; White People

Asthma guidelines use symptoms as the most important aspect of asthma control. Symptom perception varies widely between individuals. Over-perception as well as underperception of bronchoconstriction could have a negative effect on asthma management. We hypothesized that perception of bronchoconstriction in childhood asthma is not related to common measures of disease control. For that reason, we examined the clinical determinants of the perception of bronchoconstriction and the repeatability of perception measurements.. In school-age children with moderately severe atopic asthma, we measured the perception of bronchoconstriction (decrease in forced expiratory volume in 1 second (FEV(1)) during methacholine bronchoprovocation challenges. The perception of bronchoconstriction was assessed as the slope of the relation between FEV(1) and Borg score, and as the Borg score at a 20% decrease in FEV(1) from baseline during the provocation test (PS(20)). Data from subjects who had a 20% or more decrease in FEV(1) (n = 112) were used for the analysis. Fifty-four children repeated the test after 3 months. Symptoms, use of rescue medication, and peak expiratory flows were scored in diaries during the 2 weeks before testing.. Symptom perception was significantly better in children without (PD(20) > 1570 μg, n = 28) than in children with airway hyperresponsiveness (PD(20) ≤ 1570 μg, n = 112), slope 0.22 versus 0.13 respectively (p < .001). Borg scores correlated with PD(20) (p = .01), baseline FEV(1) (only for slope, p = .04), and use of rescue beta agonist (p = .01), but not with other aspects of asthma control. Repeatability of Borg scores was good (slope: R = 0.59, PS(20): R = 0.52).. Poorer symptom perception in asthmatic children correlated with hyperresponsiveness, and was associated with lower baseline FEV(1) and less use of rescue bronchodilators. This suggests that the measurement of symptom perception should be taken into account in individual management plans for children with asthma.

Topics: Adolescent; Albuterol; Androstadienes; Anti-Allergic Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstriction; Bronchodilator Agents; Child; Dyspnea; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Perception; Salmeterol Xinafoate

This 12-week study compared the efficacy and safety of a fixed combination of fluticasone propionate plus formoterol (FL/F) 250/12 μg b.i.d. administered via a dry powder inhaler (DPI) (Libbs Farmacêutica, Brazil) to a combination of budesonide plus formoterol (BD/F) 400/12 μg b.i.d. After a 2-week run-in period (in which all patients were treated exclusively with budesonide plus formoterol), patients aged 12-65 years of age (N = 196) with uncontrolled asthma were randomized into an actively-controlled, open-labeled, parallel-group, multicentre, phase III study. The primary objective was to demonstrate non-inferiority, measured by morning peak expiratory flow (mPEF). The non-inferiority was demonstrated. A statistically significant improvement from baseline was observed in both groups in terms of lung function, asthma control, and the use of rescue medication. FL/F demonstrated a statistical superiority to BD/F in terms of lung function (FEV(1)) (p = 0.01) and for asthma control (p = 0.02). Non-significant between-group differences were observed with regards to exacerbation rates and adverse events. In uncontrolled or partly controlled asthma patients, the use of a combination of fluticasone propionate plus formoterol via DPI for 12-weeks was non-inferior and showed improvements in FEV(1) and asthma control when compared to a combination of budesonide plus formoterol. (. ISRCTN60408425).

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Drug Combinations; Dry Powder Inhalers; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Treatment Outcome; Young Adult

To demonstrate the efficacy and safety of fluticasone propionate/formoterol fumarate (flutiform) in a pressurised metered-dose inhaler (pMDI) compared to two formulations of the fluticasone propionate component (Skyepharma fluticasone [SKP FP] or Flovent, GlaxoSmithKline [GSK FP]) in adults and adolescents with moderate-to-severe asthma.. Patients included in the study were ≥12 years, with symptomatic asthma for ≥1 year, steroid-requiring, had a forced expiratory volume in the first second (FEV1) of 40% to 80% (inclusive) of predicted normal values, and documented reversibility within 12 months of the study. Albuterol/salbuterol was given as rescue medication. The primary efficacy endpoint was the change in FEV1 from morning pre-dose at baseline (week 0) to 2 hours post-dose at week 12 for fluticasone/formoterol compared to SKP FP and, additionally, compared to GSK FP.. Fluticasone/formoterol was demonstrated to be statistically significantly superior to SKP FP. The least squares (LS) mean difference in FEV1 from baseline pre-dose to 2 hours post-dose at week 12 was 0.161 L (95% CI: 0.078, 0.245, p < 0.001). Fluticasone/formoterol also demonstrated superior efficacy against GSK FP (LS mean difference = 0.185 L, 95% CI: 0.102, 0.268, p < 0.001). Results from multiple secondary and tertiary efficacy endpoints assessing lung function, asthma symptoms, exacerbations and rescue medication use supported a superior efficacy of the fluticasone/formoterol combination over both fluticasone formulations. Treatment-emergent adverse events were lowest in the fluticasone/formoterol group (32.9%) compared to SKP FP (39.7%) or GSK FP (40.4%).. Results from this study demonstrate that fluticasone/formoterol 250/10 µg b.i.d. provides superior efficacy compared to fluticasone alone for the management of moderate-to-severe asthma, with a safety profile similar to that of fluticasone monotherapy.. ClinicalTrials.gov identifier: NCT00649025; EudraCT number: 2007-005653-37.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Time Factors

This study investigated the efficacy and tolerability of a new asthma therapy combining fluticasone propionate and formoterol fumarate (fluticasone/formoterol)*, administered twice daily (BID) via a single aerosol inhaler, compared with fluticasone propionate (fluticasone) or formoterol fumarate (formoterol) administered alone, in patients with mild to moderate asthma.. Patients aged ≥12 years were evenly randomized to 12 weeks of treatment with fluticasone/formoterol (100/10 µg BID), fluticasone (100 µg BID), or formoterol (10 µg BID), in this multicenter, double-blind, parallel-group, study. The 2 coprimary end points were: (1) change in forced expiratory volume in 1 second (FEV(1)) from morning predose at baseline to predose at week 12 for the comparison of the combination product with formoterol alone; and (2) change in FEV(1) from morning predose at baseline to 2 hours postdose at week 12 for the comparison of the combination product with fluticasone alone. The secondary objective was to demonstrate the efficacy of fluticasone/formoterol using other pulmonary function tests and clinical end points. Tolerability was assessed based on adverse events, clinical laboratory tests and vital sign evaluations.. Statistically significant differences were demonstrated for the 2 coprimary end points. Fluticasone/formoterol combination therapy showed significantly greater improvements from baseline to end of study in the change in predose FEV(1) compared with formoterol (least squares [LS] mean treatment difference, 0.118 L [95% CI, 0.034-0.201; P = 0.006]) and the change in predose compared with 2 hours postdose FEV(1) versus fluticasone (LS mean treatment difference, 0.122 L [95% CI, 0.040-0.204; P = 0.004]). Statistical analyses of the secondary efficacy endpoints revealed that evaluations of lung function, asthma exacerbations, asthma symptoms, rescue medication use and asthma control were supportive overall of the superior efficacy of fluticasone/formoterol combination therapy compared with its individual components; were supportive overall of the efficacy of fluticasone/formoterol combination therapy compared with its individual components. Since the secondary endpoints were analyzed using the sequential gatekeeper approach, only the mean change from baseline to final week in morning peak expiratory flow rate between the combination-therapy and formoterol groups returned statistically significant results (least squares mean difference, 20.05 [95% CI, 7.631-32.472; P = 0.002]). The fluticasone/formoterol combination therapy had a good tolerability profile over the 12-week treatment period.. Fluticasone/formoterol had a good tolerability profile and showed statistically superior efficacy for the two co-primary endpoints compared to fluticasone or formoterol, in adolescents and adults with mild to moderate asthma. ClinicalTrials.gov identifier: NCT00394199.

Topics: Adolescent; Adult; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male

A combined therapy of fluticasone propionate nasal drops (FPND) and functional endoscopic sinus surgery (FESS) can improve quality of life (QoL). When compared with prior data, the results imply that a generic measure of psychological aspects of QoL may be better than measures of respiratory symptoms and clinical parameters to capture a patient's perception of the disease and its treatment.. To better understand effects of FPND and FESS on generic QoL.. Sixty nasal polyposis patients with concomitant asthma completed participation in a randomized, double-blind, placebo-controlled, 14-week study in which they responded to the General Well-Being Schedule (GWBS).. GWBS scores (i) increased significantly after administration of FPND, independent of FESS (from lower than normal to normal), (ii) increased after FESS independent of FPND (from lower than normal to normal), and (iii) increased additively after FPND and FESS.

Topics: Adult; Aged; Androstadienes; Anti-Allergic Agents; Asthma; Double-Blind Method; Endoscopy; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps; Prospective Studies; Quality of Life; Sinusitis

To investigate the clinical benefits of 'add-on' therapy with GSK2190915 in combination with the inhaled corticosteroid (ICS) fluticasone propionate (FP) and the ICS/long-acting beta 2 agonist (LABA) combination FP/salmeterol in asthmatic subjects.. Both studies were cross-over, randomized, double-blind, double-dummy and placebo-controlled in subjects with a forced expiratory volume in 1 second (FEV1) best of >50 and ≤80% of predicted. Add-on to ICS: Subjects (n = 162) aged ≥12 years received FP 100 µg twice daily (BID) plus GSK2190915 100 mg once daily (QD); GSK2190915 300 mg QD; montelukast 10 mg QD; salmeterol 50 µg BID or placebo. Add-on to ICS/LABA: Female subjects (n = 145) aged ≥18 years received FP/salmeterol 250/50 µg BID plus GSK2190915 300 mg QD, montelukast 10 mg QD or placebo. In both studies, the primary endpoint was trough FEV1 at the end of the treatment period. Secondary endpoints included a range of objective and patient-reported measures of efficacy.. Add-on to ICS: There was no statistically significant difference in the primary endpoint between either dose of GSK2190915 (add-on to FP) and placebo. Nominally statistically significant increases were demonstrated for GSK2190915 300 mg add-on relative to placebo for mean morning peak expiratory flow (p = 0.049), percentage of symptom-free days (p = 0.035) and percentage of symptom-free 24 h periods (p = 0.030). Add-on to ICS/LABA: There were no statistically significant differences on the primary endpoint between treatment regimens. Nominally statistically significant decreases were demonstrated in daytime (p = 0.023), night-time (p = 0.041) and 24 h (p = 0.019) short-acting beta 2 agonist usage with FP/salmeterol + GSK2190915 300 mg vs. FP/salmeterol + placebo.. There was no clinically significant improvement in the primary endpoint following GSK2190915 add-on treatment; however, improvements in a range of secondary endpoints and biomarker data provided evidence of pharmacological activity. Improvements in response to background treatment may have been a limitation in both studies.. Clinicaltrials.gov identifiers: NCT01156792 and NCT01248975.

Topics: 5-Lipoxygenase-Activating Protein Inhibitors; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Albuterol; Androstadienes; Anti-Allergic Agents; Asthma; Child; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Salmeterol Xinafoate

Patients with severe refractory asthma treated with bronchial thermoplasty (BT), a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle, were followed up for 5 years to evaluate long-term safety of this procedure.. To assess long-term safety of BT for 5 years.. Patients with asthma aged 18 to 65 years requiring high-dose inhaled corticosteroids (ICSs) (>750 μg/d of fluticasone propionate or equivalent) and long-acting β2-agonists (LABAs) (at least 100 μg/d of salmeterol or equivalent), with or without oral prednisone (≤30 mg/d), leukotriene modifiers, theophylline, or other asthma controller medications were enrolled in the Research in Severe Asthma (RISA) Trial. Patients had a prebronchodilator forced expiratory volume in 1 second of 50% or more of predicted, demonstrated methacholine airway hyperresponsiveness, had uncontrolled symptoms despite taking maintenance medication, abstained from smoking for 1 year or greater, and had a smoking history of less than 10 pack-years.. Fourteen patients (of the 15 who received active treatment in the RISA Trial) participated in the long-term follow-up study for 5 years. The rate of respiratory adverse events (AEs per patient per year) was 1.4, 2.4, 1.7, and 2.4, respectively, in years 2 to 5 after BT. There was a decrease in hospitalizations and emergency department visits for respiratory symptoms in each of years 1, 2, 3, 4, and 5 compared with the year before BT treatment. Measures of lung function showed no deterioration for 5 years.. Our findings suggest that BT is safe for 5 years after BT in patients with severe refractory asthma.. clinicaltrials.gov Identifier: NCT00401986.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchi; Bronchodilator Agents; Bronchoscopy; Catheter Ablation; Female; Fluticasone; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Salmeterol Xinafoate; Young Adult

Inhaled fluticasone is used in the treatment of chronic bronchial asthma. Its high efficacy and good safety profile have been proven by clinical trials and observations. Its unique pharmacokinetic properties make it distinguishable from other drugs from this group. In vitro tests run on an artificial model of the airways and pharmacokinetic studies conducted on healthy volunteers have shown that the new formulation of this drug is outstanding due a twofold better lung deposition, compared to the reference medicine. The aim of this study was to evaluate the efficacy and safety of the new formulation of fluticasone propionate administered through new generation cyclohaler (CNG), compared to original fluticasone administered through dry powder inhaler (DPI) in patients with chronic moderate asthma.. The study included 457 patients. 376 subjects were randomized to one out of the three groups: 127 subjects--to the group treated with the new formulation of fluticasone at a dose of 125 μg BID, 125 subjects--to the group treated with new formulation of fluticasone at a dose of 250 μg BID, and 124 subjects--to the group treated with the reference drug--fluticasone DPI 500 μg BID. At the beginning of the study, the groups did not differ in demographical or clinical aspects. Active therapy lasted 12 weeks. The primary endpoint was a mean change in morning PEF during a 12-week course of therapy (ΔmPEF of 15 L/min was considered as statistically significant). Additionally, other functional parameters of the respiratory system--clinical symptoms and the use of rescue drugs were studied. During the whole study the safety of patients was monitored by recording adverse events; in addition, a systemic exposure to fluticasone was evaluated by testing the changes of cortisol in serum and in a 24-hour collection of urine in a subgroup consisting of 45 patients. Statistical analysis was conducted on both groups: intention-to-treat (ITT) and per protocol (PP).. In PP as well as in ITT analysis, a mean change in morning PEF at the end of the therapy in comparison with the initial period was statistically significant in all therapeutic groups. The efficacy of the treatment with fluticasone at doses of 125 μg BID and 250 μg and the reference medicines did not differ statistically significantly after a 12-week course of therapy or during the whole period of treatment. During the study, significant improvement in the range of other functional parameters such as evening PEF, FEV₁, clinical symptoms and the use of rescue drugs was observed in all therapeutic groups, without significant differences in efficacy between the study groups. The comparison of efficacy of fluticasone at a dose of 125 μg BID with the generic product at a dose of 250 μg BID showed a weak dose-response relationship concerning the change in morning PEF, which arises from the almost flat dose-response curve in the range of medium and high doses for this drug. No significant quantitative or qualitative differences were shown between the groups in the recorded adverse events, qualified as related to treatment with fluticasone. There were no significant changes revealed in cortisol concentration in serum or in a 24-hour collection of urine between the initial level and the final visit in any of the groups.. Fluticasone administered through the new generation cyclohaler, compared to original fluticasone DPI, allows a twofold reduction in drug dose, retaining in new formulation clinical efficacy that corresponds to the reference drug at twice the dose. New formulation of fluticasone administered through the new generation cyclohaler has a safety profile clinically comparable to the reference drug.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Chemistry, Pharmaceutical; Drug Administration Schedule; Dry Powder Inhalers; Female; Fluticasone; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Young Adult

The long-term safety of a new asthma therapy combining fluticasone propionate and formoterol fumarate (fluticasone/formoterol; flutiform(®)) was assessed.. In an open-label study, mild to moderate-severe asthmatics (≥12 years; N=472) were treated twice daily with fluticasone/formoterol 100/10 μg (n=224) or 250/10 μg (n=248) for 6 months (n=256) or 12 months (n=216). The primary and secondary objectives were the long-term safety and efficacy of fluticasone/formoterol, respectively.. In total, 413 (87.5%) patients completed the study (of which 175 participated for 12 months). Adverse events (AEs) were reported by 174 patients (36.9%): 67 (29.9%) in the 100/10 μg group and 107 (43.1%) in the 250/10 μg group. The most common AEs (>2%) were nasopharyngitis, dyspnea, pharyngitis, and headache; the majority were mild to moderate. Only 18 (3.8%) patients reported AEs considered study drug-related. Five patients per group experienced 12 serious AEs; none was study medication-related. Asthma exacerbations were reported by 53 patients (11.2%): 46 mild to moderate and nine severe. Clinical laboratory tests and vital signs showed no abnormal trends or clinically important or dose-response-related changes. The efficacy analyses showed statistically significant improvements at every time point throughout the study period at both doses.. Fluticasone/formoterol had a good safety and efficacy profile over the 6- and 12-month study periods.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Drug Administration Schedule; Drug Combinations; Ethanolamines; Europe; Female; Fluticasone; Formoterol Fumarate; Humans; Lung; Male; Middle Aged; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult

The inhaled corticosteroid, fluticasone propionate, and the long-acting β(2)-adrenergic agonist, formoterol fumarate, are both highly effective treatments for bronchial asthma. This study (NCT00393952/EudraCT number: 2006-005989-39) compared the efficacy and safety of fluticasone/formoterol combination therapy (flutiform(®); 250/10 μg) administered twice daily (b.i.d.) via a single aerosol inhaler, with the individual components (fluticasone 250 μg b.i.d.; formoterol 10 μg b.i.d.), in adult and adolescent patients with moderate-to-severe asthma.. This was a 12-week, double-blind, randomised, parallel-group, multicentre, placebocontrolled phase 3 study. The co-primary efficacy endpoints were: i) the mean change in the forced expiratory volume in the first second (FEV(1)) from morning pre-dose at baseline to pre-dose at week 12 (fluticasone/formoterol 250/10 μg vs. formoterol), ii) the mean change in FEV(1) from morning pre-dose at baseline to 2 h post-dose at week 12 (fluticasone/formoterol 250/10 μg vs. fluticasone), and iii) the number of patients who discontinued prematurely due to lack of treatment efficacy (fluticasone/formoterol 250/10 μg vs. placebo). The secondary endpoints included measures of lung function, disease control, and asthma symptoms. Safety was assessed based on adverse events, vital signs, and clinical laboratory evaluations.. Overall, 395 (70.9%) patients completed the study. Fluticasone/formoterol 250/10 μg b.i.d. was superior to the individual components and placebo for all three co-primary endpoints and demonstrated numerically greater improvements for multiple secondary efficacy analyses. Fluticasone/formoterol combination therapy had a good safety profile over the 12 weeks.. Fluticasone/formoterol combination therapy will provide clinicians with an efficacious alternative treatment option for patients with moderate-to-severe asthma.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Aged, 80 and over; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Treatment Failure; Treatment Outcome; Young Adult

The potent inhaled corticosteroid, fluticasone propionate (fluticasone), and the long-acting β2-agonist with a rapid onset of action, formoterol fumarate (formoterol), have now been combined in a single aerosol inhaler, fluticasone/formoterol (flutiform). This study investigated the efficacy and safety of fluticasone/formoterol combination therapy compared with its individual components administered concurrently via two separate inhalers.. Patients ≥ 12 years (N = 210) with mild to moderate-severe persistent, reversible asthma were evenly randomised to 12 weeks of treatment (b.i.d.) with fluticasone/formoterol combination therapy (100/10 μg b.i.d. or 250/10 μg b.i.d.) or fluticasone plus formoterol (Flixotide Evohaler, pMDI, Flovent [HFA]; Foradil, DPI, Foradil Aerolizer) administered concurrently (fluticasone + formoterol; 100 μg + 12 μg b.i.d. or 250 μg + 12 μg b.i.d.) in an open-label, parallel-group, multicentre study. The primary objective of this study was to show non-inferiority of fluticasone/formoterol compared with fluticasone + formoterol based on mean post-dose FEV1.. The mean FEV1 30-60 minutes post-dose on Day 84 was approximately 2.6 L in both the fluticasone/formoterol combination and the fluticasone + formoterol treatment groups (per protocol sets; treatment difference least squares (LS) mean: -0.03 L; 95% CI: -0.148, 0.081). The lower limit of the 95% CI (-0.148 L) was above the non-inferiority threshold of ≥-0.2 L. Analyses of other pulmonary function tests, patient reported outcomes, rescue medication use, asthma exacerbations and quality of life questionnaires were also comparable. The safety profiles of the two study groups were similar overall.. Fluticasone/formoterol combination therapy had comparable efficacy to its individual components administered concurrently, when measured by post-dose FEV1 in patients aged ≥ 12 years with mild to moderate-severe asthma. The safety and tolerability profile of fluticasone/formoterol combination therapy was similar to that of its individual components administered concurrently. Although this was an open-label study, the results remain compelling: the primary efficacy measure was a physical endpoint and study statisticians were blinded to treatment allocations until analysis was completed.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Androstadienes; Anti-Allergic Agents; Asthma; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Time Factors

Asthma affects one in eight children in the UK. National management guidelines have been available for many years but, unlike in adults, studies in children have been few, with their methodologies often based on inappropriate adult models. Sound medical evidence in support of the national guidelines for asthma management in children is lacking. The MASCOT study has been developed to address this need.. To determine whether adding salmeterol or montelukast to low-dose inhaled corticosteroids (ICSs) can reduce the number of exacerbations requiring treatment with oral corticosteroids in children with uncontrolled asthma.. A randomised, double-blind, placebo-controlled trial with a 4-week run-in period on a fluticasone propionate inhaler (100 µg twice daily) with inhaler technique correction. Patients who met the post run-in period eligibility criteria were randomised in the ratio of 1 : 1 : 1 and were followed for 48 weeks.. Secondary care hospitals based in England and Scotland with recruitment from primary and secondary care.. Children aged 6-14 years with asthma requiring frequent short-acting beta-2 agonist relief, with symptoms of asthma resulting in nocturnal wakening and/or asthma that has interfered with usual activities.. Three groups were compared: (1) inhaled fluticasone propionate 100 µg twice daily plus placebo tablet once daily; (2) inhaled fluticasone propionate 100 µg and salmeterol 50 µg twice daily (combination inhaler) plus placebo tablet once daily; and (3) inhaled fluticasone propionate 100 µg twice daily plus montelukast 5-mg tablet once daily.. The primary outcome was the number of exacerbations requiring treatment with oral corticosteroids over 48 weeks. Secondary outcome measures included quality of life as measured by the Paediatric Asthma Quality of Life Questionnaire with Standardised Activities [PAQLQ(S)] and the Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ); time from randomisation to first exacerbation requiring treatment with a short course of oral corticosteroids; school attendance; hospital admissions; amount of rescue beta-2 agonist therapy prescribed; time from randomisation to treatment withdrawal (because of lack of efficacy or side effects); lung function at 48 weeks (as assessed by spirometry); cost-effectiveness; adverse events.. The study was closed prematurely because of poor recruitment and the target sample size of 450 was not achieved. In total, 898 children were screened to enter the trial, 166 were registered for the 4-week run-in period and 63 were randomised (group 1: 19, group 2: 23, group 3: 21), with 38 contributing data for the primary outcome analysis. There were no significant differences between groups for any of the outcomes. Adverse events were similar between the groups except for nervous system disorders, which were more frequently reported on fluticasone plus montelukast.. Based on the results of the MASCOT study it is not possible to conclude whether adding salmeterol or montelukast to ICSs can reduce the number of exacerbations requiring treatment with oral corticosteroids in children with uncontrolled asthma.. Current Controlled Trials ISRCTN03556343.. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 4. See the HTA programme website for further project information.

Topics: Absenteeism; Acetates; Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Quality of Life; Quinolines; Salmeterol Xinafoate; Sulfides; United Kingdom

Many asthmatic patients are unable to quit cigarettes; therefore information is needed on treatment options for smokers. This study evaluates 10 mg/d montelukast and 250 μg of fluticasone propionate twice daily, each compared with placebo, in patients with self-reported active smoking (unable to quit) and asthma.. Patients (ages 18-55 years, with asthma [≥1 year], FEV1 of 60% to 90% of predicted value, airway reversibility [≥12%], and self-reported active smoking [≥0.5 to ≤2 packs per day]) were randomized (after a 3-week, single-blind, placebo, run-in period) to 1 of 3 parallel, 6-month, double-blind treatment arms. The primary efficacy end point was the percentage of days with asthma control during treatment. Adverse experiences (AEs) were also evaluated.. There were 347, 336, and 336 patients randomized to montelukast, fluticasone, and placebo, respectively. The mean percentage of days with asthma control over 6 months of treatment was 45% (montelukast, P < .05 vs placebo), 49% (fluticasone, P < .001 vs placebo), and 39% (placebo); the difference between montelukast and fluticasone was not significant (P = .14). Patients with a smoking history of ≤11 pack years (the median value) tended to show more benefit with fluticasone, whereas those with a smoking history of >11 pack years tended to show more benefit with montelukast. AEs occurred in similar proportions among treatment groups.. In a population of asthmatic patients actively smoking cigarettes, both 10 mg/d montelukast and 250 μg of fluticasone propionate twice daily significantly increased the mean percentage of days with asthma control compared with placebo.

Topics: Acetates; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Quinolines; Smoking; Sulfides; Young Adult

The objective of this study was to investigate whether high-dose inhaled fluticasone propionate (FP), alone or in combination with salmeterol (SAL), is as effective as oral prednisolone in reducing airway inflammation and obstruction in cats with experimentally-induced acute asthma. Six cats sensitised to Ascaris suum (AS) were enrolled in a prospective controlled therapeutic trial and underwent four aerosol challenges, at 1-month intervals with AS allergen. The allergen - stimulated animals received four consecutive days treatment with either oral prednisolone at 1mg/kg twice daily, 500 μg of FP inhaled twice daily, or a combination of FP/SAL at 500 μg/50 μg inhaled twice daily, respectively, according to a randomised cross-over design. Treatment-related changes in lung function, airway responsiveness (AR) and bronchoalveolar lavage fluid (BALF) cytology were assessed. Barometric whole-body plethysmography (BWBP) was used for the assessment of respiratory variables and AR. No significant differences in respiratory rate or Penh (an estimate of airflow limitation measured by BWBP) were detected among treatment groups. Allergen-induced airway hyper-responsiveness was significantly inhibited by all three steroid treatments (P<0.05). The mean BALF eosinophil percentage (±SEM) was lower after oral and inhaled corticosteroid treatment and these changes were significant for groups receiving prednisolone and the FP/SAL combination. Findings suggest high-dose FP, particularly in combination with SAL, is effective in ameliorating airway inflammation and hyper-responsiveness in this model of acute feline asthma, and highlight the potential use of these drugs in cats experiencing acute exacerbations of the naturally occurring disease.

Topics: Administration, Inhalation; Administration, Oral; Albuterol; Allergens; Androstadienes; Animals; Anti-Inflammatory Agents; Antigens, Helminth; Ascaris suum; Asthma; Bronchodilator Agents; Cat Diseases; Cats; Cross-Over Studies; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Male; Prednisolone; Prospective Studies

Previous studies in adults with asthma incorporating the control of sputum eosinophils into management strategies have shown significant reductions in exacerbations. A study was undertaken to investigate whether this strategy would be successful in children with severe asthma.. 55 children (7-17 years) with severe asthma were randomised to either a conventional symptom-based management strategy or to an inflammation-based strategy (principally sputum eosinophils). Children were seen 3-monthly over a 1-year period.. The annual rate of total and major exacerbations (courses of oral corticosteroids) was non-significantly lower in the inflammatory management group compared with the symptom management group (3.6 vs. 4.8, incident rate ratio (IRR) 0.75, 95% CI 0.54 to 1.04, p=0.082; and 1.9 vs. 2.7 IRR 0.73, 95% CI 0.42 to 1.28, p=0.274 for total and major exacerbations, respectively). Significantly fewer subjects in the inflammatory management group experienced an exacerbation within 28 days of a study visit. There were small non-significant differences in measures of asthma control (symptom-free days and short-acting β agonist use) favouring the inflammatory management group. There was no significant difference in the inhaled corticosteroid dose prescribed over the course of the study.. Incorporating the control of sputum eosinophils into the management algorithm did not significantly reduce overall exacerbations or improve asthma control. Exacerbations were reduced in the short term, suggesting that more frequent measurements would be needed for a clinically useful effect and that controlling inflammation may have a role to play in subgroups of children with severe asthma.

Topics: Adolescent; Adrenergic beta-Agonists; Algorithms; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Eosinophils; Female; Fluticasone; Glucocorticoids; Humans; Leukocyte Count; Male; Sputum

We determined lung bioavailability of a fluticasone propionate (FP) pressurised metred-dose inhaler (Flovent HFA; GlaxoSmithKline, Research Triangle Park, NC, USA) administered via AeroChamber Plus (Monaghan Medical, Plattsburgh, NY, USA) with Facemask and Babyhaler (GlaxoSmithKline) valved holding chambers (VHCs) using a population pharmacokinetic approach. Children from 1 to <4 yrs of age with stable asthma but a clinical need for inhaled corticosteroid therapy were administered 88 μg FP hydrofluoroalkane (2 × 44 μg) twice daily delivered through the two devices in an open-label, randomised crossover manner for 8 days each. Patients were randomised to one of three sparse sampling schedules for blood collection throughout the 12-h dosing interval on the 8th day of each treatment for pharmacokinetic analysis. The area under the FP plasma concentration-time curve (AUC) was determined for each regimen. 17 children completed the study. The population mean AUC following FP with AeroChamber Plus with Facemask was 97.45 pg·h·mL(-1) (95% CI 85.49-113.32 pg·h·mL(-1)) and with Babyhaler was 51.55 pg·h·mL(-1) (95% CI 34.45-64.46 pg·h·mL(-1)). The relative bioavailability (Babyhaler/AeroChamber Plus) was 0.53 (95% CI 0.30-0.75). Clinically significant differences in lung bioavailability were observed between the devices. VHCs are not interchangeable, as differences in drug delivery to the lung may occur. A population pharmacokinetic approach can be used to determine lung bioavailability of FP.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Area Under Curve; Asthma; Biological Availability; Bronchodilator Agents; Child, Preschool; Cross-Over Studies; Drug Administration Schedule; Equipment Design; Female; Fluticasone; Hospitals, Pediatric; Humans; Infant; Lung; Male; Nebulizers and Vaporizers

The airway contains airway smooth muscle and airway vascular smooth muscle. The acute effects of inhaled long-acting β(2)-adrenergic agonists (LABAs) alone, or in combination with an inhaled glucocorticoid (ICS), on airway smooth muscle tone in asthma are known; however, to the best of our knowledge, their effect on airway vascular smooth muscle tone has not been investigated previously. The objective of this study was to investigate the immediate effects of a LABA and an ICS alone and in combination on airway blood flow (Qaw) as an index of airway vascular smooth muscle tone in patients with stable asthma.. Fourteen subjects with moderate asthma inhaled single doses of salmeterol (50 μg), fluticasone propionate (250 μg), salmeterol/fluticasone propionate (50/250 μg), or placebo; Qaw was measured before and serially for 240 min after drug administration.. Mean Qaw increased after salmeterol and salmeterol/fluticasone propionate, with peaks at 60 min of 34% and 40%, respectively, and returned to baseline by 240 min after inhalation. Fluticasone propionate alone caused a transient decrease in mean Qaw. The maximal changes in Qaw, which occurred at different times, were 60% for salmeterol, 67% for salmeterol/fluticasone propionate, and -19% for fluticasone propionate (P < .05 vs placebo for all).. The LABA salmeterol has an acute vasodilator action on the airway of subjects with stable asthma. The addition of fluticasone propionate, which by itself causes vasoconstriction, does not attenuate the salmeterol-induced vasodilation, suggesting that fluticasone propionate potentiates the vasodilator effect of salmeterol. The vasodilation could be of clinical benefit by promoting the vascular clearance of inflammatory mediators including spasmogens from the airway.. ClinicalTrials.gov; No.: NCT01231230; URL: www.clinicaltrials.gov.

Topics: Administration, Inhalation; Adult; Airway Resistance; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Blood Flow Velocity; Bronchi; Bronchodilator Agents; Delayed-Action Preparations; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Muscle, Smooth; Muscle, Smooth, Vascular; Salmeterol Xinafoate; Vasodilation; Vital Capacity; Young Adult

An important function of the healthy nose is the ability to adjust nasal patency in response to stimuli such as a change in posture between sitting and supine. We hypothesised that the regulation of nasal patency would be impaired in patients with asthma and mild rhinitis and that it could be improved by reducing nasal inflammation with a topical nasal steroid. This is a randomised, placebo-controlled, double-blind, cross-over study comprising 19 subjects with well-controlled asthma and a history of rhinitis without current treatment. The subjects were randomised to fluticasone propionate aqueous nasal spray (Beconase(®)), 200 μg daily, or placebo (FESS(®) saline nasal spray), for 6 weeks in a cross-over design with a 4-week wash-out between treatments. Nasal patency was measured with acoustic rhinometry, while sitting and supine and with peak nasal inspiratory flow (PNIF). Treatment response was also monitored with spirometry, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Short Form-36 (SF-36), and The Pittsburgh Sleep Quality Index. The minimal cross-sectional area remained unchanged between sitting and supine at baseline and after placebo but after fluticasone propionate there was a significant decrease. PNIF, RQLQ and SF-36 improved after fluticasone propionate, whereas sleep quality did not change. In well-controlled asthma and mild rhinitis, nasal steroid treatment normalised the neurovascular response to posture in the nasal mucosa and improved health-related quality of life. An impaired ability to regulate nasal patency could be a marker of upper airway inflammation in patients with asthma that can be measured non-invasively.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Allergic Agents; Asthma; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Follow-Up Studies; Humans; Male; Nasal Mucosa; Prospective Studies; Quality of Life; Rhinitis; Rhinometry, Acoustic; Severity of Illness Index; Treatment Outcome

To investigate the influence of an incentive device, the Funhaler, on spacer technique and symptom control in young children with asthma and recurrent wheeze.. Randomised controlled trial where 132 2-6 year old asthmatic children received regular inhaled fluticasone through Aerochamber Plus, or Funhaler. The setting was a research clinic at Princess Margaret Hospital for Children, Perth, Australia. Subjects were followed up for a year. The main outcome measure was asthma symptoms. Proficiency in spacer technique was measured as salbutamol inhaled from spacer onto filter. Quality of life was measured every three months. Groups were compared in terms of spacer technique, symptoms and quality of life. The relationship between spacer technique and clinical outcome was examined.. There was no difference between Funhaler and Aerochamber groups in wheeze free days, cough free days, bronchodilator free days or quality of life (P = 0.90, 0.87, 0.74 and 0.11 respectively). Spacer technique was better in the Funhaler group (P = 0.05), particularly in subjects younger than 4 years of age (P = 0.002). Drug dose on filter (as the mean of five 100 mg doses) ranged from zero to 136 mg.. Use of Funhaler incentive device does not improve clinical outcome, but improves spacer technique in children younger than 4 years. Variability in drug delivery is large in young children using pressurised metered dose inhalers and spacers.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Asthma; Bronchodilator Agents; Child; Child, Preschool; Equipment Design; Feedback; Female; Fluticasone; Follow-Up Studies; Humans; Male; Metered Dose Inhalers; Outcome Assessment, Health Care; Western Australia

While most of the clinical benefits of inhaled corticosteroid (ICS) therapy may occur at low doses, results of dose-ranging studies are inconsistent. Although symptom/lung function response to low and high dose ICS medication is comparable, it is uncertain whether low dose ICSs are as effective as high dose in the treatment of inflammation and remodeling.. 22 mild or moderate asthmatic adult subjects (corticosteroid free for > 2 months) participated in a randomized, parallel group study to compare effects of fluticasone propionate (FP) 200 mcg/day and 1000 mcg/day. Alveolar macrophage (AM)-derived cytokines and basement membrane thickness (BMT) were measured at baseline and after 7 weeks treatment while symptoms, spirometry, exhaled nitric oxide (eNO) and airway hyperresponsiveness (AHR) to mannitol at baseline and 6 weeks.. FP improved spirometry, eNO, symptoms and AHR with no difference between low and high dose FP. Both high and low dose FP reduced GM-CSF, TNF-alpha and IL-1ra, with no change in BMT and with no differences between low and high dose FP.. 200 μg/day of FP was as effective as 1000 μg/day in improving asthma control, airway inflammation, lung function and AHR in adults in the short term. Future studies should examine potential differential effects between low and high dose combination therapy (ICS/long acting beta agonist) on inflammation and airway remodeling over longer treatment periods.

Topics: Administration, Inhalation; Adolescent; Adult; Airway Remodeling; Androstadienes; Anti-Asthmatic Agents; Asthma; Basement Membrane; Breath Tests; Cytokines; Female; Fluticasone; Humans; Inflammation; Lung; Macrophages, Alveolar; Male; Mannitol; Nitric Oxide; Respiratory Function Tests; Young Adult

This randomized, double-blind, multicenter study was designed to evaluate the efficacy of inhaled once-daily fluticasone furoate (FF) administered in the evening in patients with persistent asthma not controlled by short-acting beta(2) agonists, and to determine the dose(s) suitable for further development.. Of 1459 patients screened, 598 received one of six treatments: placebo, FF (25 μg, 50 μg, 100 μg or 200 μg) once daily each evening, or fluticasone propionate (FP) 100 μg twice daily for 8 weeks. The primary endpoint was change from baseline in pre-dose evening forced expiratory volume in 1 s (FEV(1)).. A dose-response effect was observed for once-daily FF 25-200 μg including (p < 0.001) and excluding placebo (p = 0.03). FF 50-200 μg once daily significantly increased FEV(1) from baseline (p < 0.05 vs placebo), by >200 mL for FF 100 μg and 200 μg. Significant improvements were also achieved for peak expiratory flow, and percentage symptom-free and rescue-free 24 h periods. The magnitude of effect was at least as good as twice-daily FP. Overall, once-daily FF was well tolerated with no systemic corticosteroid effects.. FF 50-200 μg/day once daily in the evening demonstrated dose-related efficacy in asthma with 100-200 μg appearing to be the optimal doses for further evaluation. ClinicalTrials.gov: NCT00603382.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Treatment Outcome; Young Adult

Two distinct, stable inflammatory phenotypes have been described in adults with asthma: eosinophilic and non-eosinophilic. Treatment strategies based on these phenotypes have been successful. This study evaluated sputum cytology in children with asthma to classify sputum inflammatory phenotypes and to assess their stability over time.. Sputum induction was performed in 51 children with severe asthma and 28 with mild to moderate asthma. Samples were classified as eosinophilic (>2.5% eosinophils), neutrophilic (>54% neutrophils); mixed granulocytic (>2.5% eosinophils, >54% neutrophils); or paucigranulocytic (≤2.5% eosinophils, ≤54% neutrophils). Sputum induction was repeated every 3 months in children with severe asthma (n=42) over a 1-year period and twice in mild to moderate asthma (n=17) over 3-6 months.. 62 children (78%) had raised levels of inflammatory cells in at least one sputum sample. In the longitudinal analysis 37 of 59 children (63%) demonstrated two or more phenotypes. Variability in sputum inflammatory phenotype was observed in both the severe and the mild to moderate asthma groups. Change in phenotype was not related to change in inhaled corticosteroid (ICS) dose or asthma control, nor was it reflected in a change in exhaled nitric oxide (FE(NO)). 24 children (41%) fulfilled the criteria for non-eosinophilic asthma on one occasion and eosinophilic on another. There were no differences in severity, asthma control, atopy, ICS dose or forced expiratory volume in 1 s between those who were always non-eosinophilic and those always eosinophilic.. Raised levels of inflammatory cells were frequently found in children with asthma of all severities. Sputum inflammatory phenotype was not stable in children with asthma.

Topics: Adolescent; Androstadienes; Asthma; Child; Dose-Response Relationship, Drug; Eosinophilia; Female; Fluticasone; Glucocorticoids; Humans; Inflammation; Longitudinal Studies; Male; Neutrophils; Phenotype; Severity of Illness Index; Sputum; Treatment Outcome

Combination therapy with an inhaled corticosteroid (ICS) and a long-acting β(2)-agonist (LABA) in a single inhaler is the mainstay of asthma management and salmeterol/fluticasone combination (SFC) and fixed-dose formoterol/budesonide combination (FBC) are currently available in Japan; however, there is nothing to choose between the two. The purpose of this study was to clarify the effect of switching from SFC to FBC in patients with asthma not adequately controlled under the former treatment regimen.. This was a prospective, multicenter, open-label, uncontrolled longitudinal study in 87 adult patients with an Asthma Control Questionnaire, 5-item version (ACQ5) score of greater than 0.75 under treatment with SFC 50/250μg one inhalation twice daily (bid). SFC was switched to FBC 4.5/160μg two inhalations bid. Study outcomes included ACQ5 score, peak expiratory flow (PEF), FEV(1), and fractional exhaled nitric oxide (FeNO) at the end of treatment period.. Eighty-three patients completed the study. ACQ5 scores improved and exceeded the clinically meaningful difference after 12 weeks of treatment and well-controlled asthma (ACQ5 score ≤0.75) was attained in 37 (44.6%) patients. Minimum and maximum PEF and FEV(1) values improved significantly, but not FeNO values, after switching from SFC to FBC.. Switching ICS/LABA combination therapy is a useful option in the management of asthma that is not optimally controlled.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Budesonide; Drug Substitution; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Respiratory Function Tests; Salmeterol Xinafoate; Treatment Failure; Young Adult

Treatment guidelines recommend using an inhaled corticosteroid (ICS) plus a long-acting β(2)-agonist (LABA) for childhood asthma when the symptoms are not controlled by ICS alone, but the appropriate use of LABAs in children continues to be debated.. To compare the efficacy of an inhaled salmeterol and fluticasone propionate combination, 50/100 μg twice daily, with fluticasone propionate, 100 μg twice daily, or salmeterol, 50 μg twice daily, in children with multiple-trigger wheeze.. A total of 105 children 4 to 7 years of age with multiple-trigger wheezing based on respiratory symptoms and bronchodilator responsiveness and/or exercise-induced bronchoconstriction without a viral cold were randomized to salmeterol-fluticasone, fluticasone propionate alone, or salmeterol alone via a metered-dose inhaler and a spacer device for 8 weeks. The primary efficacy outcome was exhaled nitric oxide level. Secondary outcomes were lung function measurements via impulse oscillometry, respiratory symptoms, and rescue medication use.. The exhaled nitric oxide levels decreased after all treatments, significantly more so after salmeterol-fluticasone and fluticasone than with salmeterol (adjusted geometric means at 8 weeks: salmeterol-fluticasone, 9.4 ppb; fluticasone, 9.3 ppb; salmeterol, 13.9 ppb; salmeterol-fluticasone vs salmeterol, P = .02; fluticasone vs salmeterol, P = .01). No treatment differences were found with respect to respiratory symptoms or median rescue use. Salmeterol-fluticasone resulted in a small but statistically significant improvement in baseline lung function compared with fluticasone. All treatments were equally well tolerated.. The effects of salmeterol-fluticasone and fluticasone were comparable, although lung function improvement was better with salmeterol-fluticasone than with fluticasone alone. There is no obvious benefit in initiation therapy with salmeterol-fluticasone rather than fluticasone alone in the treatment of steroid-naive children with multiple-trigger wheeze.. Pathway of clinical trial registry of Helsinki University:http://www.hus.fi/?Path=1;28;2530;9899;9900;23618;23903;33578.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Asthma; Breath Tests; Bronchodilator Agents; Child; Child, Preschool; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Male; Nitric Oxide; Precipitating Factors; Respiratory Sounds; Salmeterol Xinafoate; Treatment Outcome

Symptomatic, steroid-naïve asthmatic patients may have low sputum eosinophil numbers. The aim of the study was to determine whether low sputum eosinophil numbers persisted over time, during treatment with salmeterol monotherapy.. Forty steroid-naïve, symptomatic asthmatic patients, with sputum eosinophils <3%, were randomized to receive open-label salmeterol (50 µg twice a day, n = 30) or fluticasone (125 µg twice a day, n = 10) and were then assessed at 1, 3 and 6 months. All patients underwent spirometry, a methacholine challenge test and sputum induction at each visit. Symptom scores and peak expiratory flow were recorded throughout the study. Patients were permitted to withdraw from the study at any time, if they experienced exacerbations or deterioration of symptoms.. The average sputum eosinophil percentage remained normal (≤1.9%) in both groups over the study period. The eosinophil percentages were ≤1.9% in 65 of the 80 samples obtained from salmeterol-treated patients throughout the study period. Eight patients had an asthma exacerbation or deterioration, during which one developed sputum eosinophilia. Twelve patients, 11 of whom were randomized to salmeterol and one to fluticasone, developed transient sputum eosinophilia at least once during the study. This was not associated with asthma exacerbation (except for one patient). Sputum neutrophil percentage did not change in either group.. Low sputum eosinophil numbers persisted over 6 months in a majority of patients with non-eosinophilic asthma who received salmeterol monotherapy. However, transient sputum eosinophilia occurred in 40% indicating that non-eosinophilic asthma may not be a stable phenotype.

Topics: Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Eosinophilia; Female; Fluticasone; Humans; Male; Methacholine Chloride; Middle Aged; Neutrophils; Salmeterol Xinafoate; Sputum; Young Adult

This study investigated the efficacy and safety of a new asthma therapy combining fluticasone propionate and formoterol fumarate (fluticasone/formoterol; flutiform®), administered twice daily (b.i.d.) via a single aerosol inhaler, compared with its individual components administered separately and placebo, in patients with mild-to-moderate asthma.. Patients aged ≥ 12 years were evenly randomised to 12 weeks of treatment with fluticasone/formoterol (100/10 μg b.i.d.), fluticasone (100 μg b.i.d.), formoterol (10 μg b.i.d.), or placebo, in this double-blind, parallel group, multicentre study. The three co-primary endpoints were: a) change in forced expiratory volume in the first second (FEV(1)) from morning pre-dose at baseline to pre-dose at week 12 for the comparison with formoterol; b) change in FEV(1) from morning pre-dose at baseline to 2 hours post-dose at week 12 for the comparison with fluticasone, and c) time to discontinuation due to lack of efficacy from baseline to week 12 for the comparison with placebo. Safety was assessed based on adverse events, clinical laboratory tests and vital sign evaluations.. Statistically significant differences were demonstrated for all the three co-primary endpoints. Fluticasone/formoterol combination therapy showed significantly greater improvements from baseline to end of study in the change in pre-dose FEV(1) compared with formoterol (Least Squares (LS) mean treatment difference: 0.101 L; 95% Confidence Interval (CI): 0.002, 0.199; p = 0.045) and the change in pre-dose compared with 2 hours post-dose FEV(1) versus fluticasone (LS mean treatment difference: 0.200 L; 95% CI: 0.109, 0.292; p < 0.001). The time to discontinuation due to lack of efficacy was significantly longer for patients in the combination therapy group compared with those receiving placebo (p = 0.015). Overall, the results from multiple secondary endpoints assessing lung function, asthma symptoms, and rescue medication use supported the superior efficacy of the combination product compared with fluticasone, formoterol, and placebo. The fluticasone/formoterol combination therapy had a good safety and tolerability profile over the 12 week treatment period.. Fluticasone/formoterol had a good safety and tolerability profile and showed statistically superior efficacy for the three co-primary endpoints compared to fluticasone, formoterol, and placebo, in adolescents and adults with mild-to-moderate asthma. EudraCT number: 2007-002866-36; US NCT number: NCT00393991.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Asthma; Bronchodilator Agents; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Europe; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; North America; Respiratory Function Tests; Severity of Illness Index; Treatment Outcome; Young Adult

The inhaled corticosteroid, fluticasone propionate (fluticasone), and the long-acting beta(2)-agonist, formoterol fumarate (formoterol), have been combined in a single aerosol inhaler (fluticasone/formoterol). In a randomized, open-label study, fluticasone/formoterol showed similar efficacy to fluticasone/salmeterol after 12 weeks of treatment. This post-hoc analysis compared the onset of bronchodilation with the two treatments.. Adults with mild-to-moderate-severe persistent asthma were randomized to fluticasone/formoterol (100/10 or 250/10 μg twice daily [b.i.d.]) or fluticasone/salmeterol (100/50 or 250/50 μg b.i.d.) for 12 weeks. The onset of bronchodilation (the first post-dose time point at which the forced expiratory volume in 1 second [FEV(1)] was ≥12% greater than the pre-dose value), responder rates (the proportion of patients achieving bronchodilation), and changes in FEV(1) were assessed at days 0 (baseline) and 84.. Fluticasone/formoterol (n = 101) provided more rapid onset of bronchodilation than fluticasone/salmeterol (n = 101) over the first 120 min post-dose on days 0 (hazard ratio [HR] = 1.47 [95% CI 1.05-2.05]) and 84 (HR = 1.77 [95% CI 1.14-2.73]). The odds of a patient achieving bronchodilation within 5 min of dosing were almost four-times higher with fluticasone/formoterol than with fluticasone/salmeterol on day 0 (odds ratio [OR] = 3.97 [95% CI 1.96-8.03]) and almost 10-times higher on day 84 (OR = 9.58 [95% CI 2.14-42.90]); the odds of achieving bronchodilation within 120 min post-dose were approximately twofold higher with fluticasone/formoterol on both days. The overall percentage increase in least-squares (LS) mean FEV1 during the 120-min post-dose period was significantly greater with fluticasone/formoterol than fluticasone/salmeterol on days 0 (LS mean treatment difference: 4.70% [95% CI 1.57-7.83]; P = 0.003) and 84 (2.79% [95% CI 0.65-4.93]; P = 0.011).. These analyses showed that fluticasone/formoterol provided a faster onset of bronchodilation than fluticasone/salmeterol, which was maintained over 12 weeks of treatment. This benefit may facilitate treatment adherence among patients with asthma.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Follow-Up Studies; Forced Expiratory Volume; Formoterol Fumarate; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Odds Ratio; Risk Assessment; Severity of Illness Index; Time Factors; Treatment Outcome

The inhaled corticosteroid fluticasone propionate (fluticasone) and the long-acting β₂ agonist formoterol fumarate (formoterol) have been combined in a single aerosol inhaler fluticasone/formoterol (flutiform(®)). This study compared the efficacy and safety of fluticasone/formoterol with the combination product budesonide/formoterol (Symbicort(®) Turbohaler(®)).. A randomized, double-blind, double-dummy, multicenter, Phase 3 study comprising a 7- (± 3) day screening, 2-4-week run-in, and 12-week treatment periods. Patients aged ≥ 12 years with moderate to severe persistent asthma for ≥ 6 months before screening and forced expiratory volume in one second (FEV₁) 50-80% predicted and ≥ 15% reversibility following salbutamol inhalation were randomized to fluticasone/formoterol 250/10 μg twice daily (n = 140) or budesonide/formoterol 400/12 μg twice daily (n = 139).. Fluticasone/formoterol was comparable to budesonide/formoterol with respect to the primary endpoint, change in pre-dose FEV₁ from baseline to Week 12. The LS mean treatment difference was -0.044 L, with a lower 95% confidence interval (CI) greater than the pre-defined non-inferiority limit of -0.2 L (95% CI: -0.130, 0.043 L; p < 0.001). Non-inferiority was also demonstrated for the secondary endpoints mean change in FEV₁ from baseline (pre-dose) to 2 hours post-dose at Week 12, and discontinuations due to lack of efficacy. Similar results were obtained for both treatment groups for all other secondary endpoints. Fluticasone/formoterol had a good safety profile that was comparable with budesonide/formoterol.. This study demonstrated comparable efficacy of fluticasone/formoterol to budesonide/formoterol in terms of the primary endpoint, change in pre-dose FEV₁ from baseline to Week 12. This was supported by comparable results for both treatments for all secondary endpoints.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Dry Powder Inhalers; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Young Adult

International guidelines advocate a standard approach to asthma management for all, despite its heterogeneity. "Personalized" treatment of inflammatory asthma phenotypes confers superior benefits. We wished to evaluate dose response to inhaled corticosteroids (ICSs) in patients with asthma with an elevated fractional exhaled nitric oxide (Feno) phenotype using domiciliary measurements.. We performed a randomized, crossover trial in 21 patients with mild to moderate persistent asthma receiving ICSs with elevated Feno (>30 parts per billion [ppb]) that increased further (>10 ppb) after ICS washout. Patients were randomized to 2 weeks of either fluticasone propionate 50 μg bid (FP100) or 250 μg bid (FP500). The primary outcome was response in diurnal domiciliary Feno levels. Secondary outcomes included mannitol challenge, serum eosinophilic cationic protein (ECP), blood eosinophil count, and asthma control questionnaire.. We found significant dose-related reductions of diurnal Feno compared with baseline - morning Feno: baseline = 71 ppb (95% CI, 61-83 ppb); FP100 = 34 ppb (95% CI, 29-40 ppb), P < .001; FP500 = 27 ppb (95% CI, 22-33 ppb), P < .001; and significant dose separation for morning, P < .05, and evening, P < .001. Time-series Feno displayed exponential decay: FP100 R² = 0.913, half-life = 69 h (95% CI, 50-114 h); FP500 R² = 0.966, half-life = 55 h (95% CI, 45-69 h), as well as diurnal variation. The Asthma Control Questionnaire showed significant improvements exceeding the minimal important difference (>0.5) with values in keeping with controlled asthma (<0.75) after each dose: FP100 = 0.48 (95% CI, 0.24-0.71), P = .004; FP500 = 0.37 (95% CI, 0.18-0.57), P = .001. All other secondary inflammatory related outcomes (mannitol, ECP, and eosinophils) showed significant improvements from baseline but no dose separation.. There is a significant dose response of diurnal Feno to ICS in patients with asthma with an elevated Feno phenotype, which translates into well-controlled asthma. Further interventional studies are warranted using domiciliary Feno in this specific phenotype.. ClinicalTrials.gov; No.: NCT00995657; URL: clinicaltrials.gov.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Asthma; Bronchodilator Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Exhalation; Female; Fluticasone; Home Care Services; Humans; Male; Middle Aged; Nitric Oxide; Phenotype; Surveys and Questionnaires; Treatment Outcome; Young Adult

Small airways are an important site of inflammation and obstruction in asthma, which contributes to the severity of airway hyperresponsiveness (AHR) that is usually measured by nebulisation of large-particle stimuli. We investigated whether small and large particle sizes of aerosolised adenosine monophospate (AMP) provoke similar severity of AHR. Additionally, effects of the small-particle inhaled corticosteroid (ICS) ciclesonide and large-particle ICS fluticasone on AHR to large- and small-particle size AMP were assessed. After a 4-week run-in period using open-label fluticasone (100 μg b.i.d.), 37 mild-to-moderate asthmatics underwent provocations with standard-size (3.7 μm), large-particle (9.9 μm) and small-particle (1.06 μm) AMP. Subjects received 4-week ciclesonide (160 μg s.i.d.) or fluticasone (100 μg b.i.d.) treatment (double-blind and double-dummy) followed by large- and small-particle AMP provocation. Small-particle AMP induced a 20% decrease in forced expiratory volume in 1 s (FEV(1)) at a significantly higher dose than large-particle AMP. Ciclesonide and fluticasone had comparable effects on AMP provocations. Not all subjects reached the provocative concentration causing a 20% fall in FEV(1) (PC(20)) at the highest AMP dose. In those who did, ciclesonide improved small-particle AMP PC(20) by 1.74 doubling doses (DD) (p = 0.03), whereas fluticasone did not. Conversely, fluticasone improved large-particle AMP PC(20) significantly (1.32 DD; p = 0.03), whereas ciclesonide did not. Small-particle AMP provocation appears to be a promising tool to assess changes in small airway inflammation. Future adjustments are necessary taking into account the very small particle size used, with large exhaled fractions. In asthmatics reaching a PC(20) with small- and large-particle AMP provocations, ciclesonide improves hyperresponsiveness to small particle size AMP, and fluticasone to large particle size. This warrants further research to target provocations and treatment to specific airway sizes.

Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Inflammation; Male; Nebulizers and Vaporizers; Nitric Oxide; Particle Size; Spirometry

An acute-care visit for asthma often signals a management failure. Although a written action plan is effective when combined with self-management education and regular medical review, its independent value remains controversial.. We examined the efficacy of providing a written action plan coupled with a prescription (WAP-P) to improve adherence to medications and other recommendations in a busy emergency department.. We randomized 219 children aged 1-17 years to receive WAP-P (n = 109) or unformatted prescription (UP) (n = 110). All received fluticasone and albuterol inhalers, fitted with dose counters, to use at the discretion of the emergency physician. The main outcome was adherence to fluticasone (use/prescribed × 100%) over 28 days. Secondary outcomes included pharmacy dispensation of oral corticosteroids, β(2)-agonist use, medical follow-up, asthma education, acute-care visits, and control.. Although both groups showed a similar drop in adherence in the initial 14 days, adherence to fluticasone was significantly higher over Days 15-28 in children receiving WAP-P (mean group difference, 16.13% [2.09, 29.91]). More WAP-P than UP patients filled their oral corticosteroid prescription (relative risk, 1.31 [1.07, 1.60]) and were well-controlled at 28 days (1.39 [1.04, 1.86]). Compared with UP, use of WAP-P increased physicians' prescription of maintenance fluticasone (2.47 [1.53, 3.99]) and recommendation for medical follow-up (1.87 [1.48, 2.35]), without group differences in other outcomes.. Provision of a written action plan significantly increased patient adherence to inhaled and oral corticosteroids and asthma control and physicians' recommendation for maintenance fluticasone and medical follow-up, supporting its independent value in the acute-care setting. Clinical trial registered with www.clinicaltrials.gov (NCT 00381355).

Topics: Adolescent; Adrenal Cortex Hormones; Advance Care Planning; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Child Health Services; Child, Preschool; Drug Prescriptions; Emergency Service, Hospital; Fluticasone; Follow-Up Studies; Humans; Infant; Nebulizers and Vaporizers; Patient Compliance; Pediatrics; Self Care; Single-Blind Method; Treatment Outcome

Patients with mild persistent asthma constitute about 70% of the asthma population; thus, it is important to know which first-line treatment is best for the management of mild asthma. We compared benefits of first-line treatment with ciclesonide and a combination of fluticasone and salmeterol in patients with mild asthma.. Patients aged 12 to 75 years with mild persistent asthma were enrolled in a randomized, double-blind, placebo-controlled study. After run-in, patients were randomized to ciclesonide 160 μg once daily (CIC160), fluticasone propionate/salmeterol 100/50 μg bid (FP200/S100), or placebo for 52 weeks. The primary variable was time to first severe asthma exacerbation; the coprimary variable was the percentage of poorly controlled asthma days. Patients recorded asthma symptoms and salbutamol use in electronic diaries and completed a standardized version of the Asthma Quality of Life Questionnaire.. Compared with placebo, the time to first severe asthma exacerbation was prolonged, and lung function was improved with FP200/S100 treatment (P = .0002) but not with CIC160. Both CIC160 and FP200/S100 provided significantly fewer poorly controlled asthma days than placebo (P ≤ .0016 for both active treatments). Moreover, both active treatments provided significantly more asthma symptom-free days (P ≤ .0001), rescue medication-free days (P = .0005, one-sided), and days with asthma control (P ≤ .0033). Overall Asthma Quality of Life Questionnaire scores were significantly higher in both active treatment groups than placebo (P ≤ .0017).. In mild asthma, FP200/S100 prolonged time to first severe asthma exacerbation, and CIC160 and FP200/S100 were clinically equieffective for most measures of asthma control.. ClinicalTrials.gov; No.: NCT00163358; URL: www.clinicaltrials.gov.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Placebos; Pregnenediones; Quality of Life; Respiratory Function Tests; Salmeterol Xinafoate; Statistics, Nonparametric; Surveys and Questionnaires; Treatment Outcome

Fluticasone and formoterol are well established medications for the treatment of asthma. This study (Clinicaltrials.gov identifier: NCT00734318) compares the efficacy and safety of a combination of these drugs in a single inhaler (fluticasone/formoterol) versus the individual components (fluticasone + formoterol).. Patients aged ≥ 18 years (n=620) with a history of severe, persistent reversible asthma for ≥ 6 months prior to screening were included in this randomized, double-blind study, which consisted of a screening phase of up to 5 days, a 2-week run-in phase and an 8-week treatment period.. Fluticasone/formoterol (500/20 μg, b.i.d.) was at least as effective as fluticasone + formoterol (500 μg + 24 μg, b.i.d.) with respect to the primary outcome measure: there were similar increases in mean pre-morning dose forced expiratory volume in the first second (FEV(1)) in these two groups. Fluticasone/formoterol (500/20 μg, b.i.d.) also demonstrated similar efficacy to fluticasone + formoterol in terms of change in mean FEV(1) from baseline pre-morning dose to 2 h post-morning dose at week 8, as well as for several secondary parameters. Fluticasone/formoterol (500/20 μg, b.i.d.) demonstrated superiority to fluticasone monotherapy (500 μg, b.i.d.) and fluticasone/formoterol (100/10 μg, b.i.d.) for several secondary efficacy parameters. Fluticasone/formoterol had a similar safety and tolerability profile to fluticasone + formoterol.. This study demonstrated that the fluticasone/formoterol combination is at least as effective as its components administered concurrently from separate inhalers. Fluticasone/formoterol (500/20 μg, b.i.d.) showed superior efficacy to its inhaled corticosteroid component alone and the efficacy of fluticasone/formoterol was dose-dependent for several clinically important parameters.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Asthmatic Agents; Asthma; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Epidemiologic Methods; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Nebulizers and Vaporizers; Treatment Outcome; Young Adult

Cost-effectiveness analyses of asthma controller regimens for adults exist, but similar evaluations exclusively for children are few.. We sought to compare the cost-effectiveness of 2 commonly used asthma controllers, fluticasone and montelukast, with data from the Pediatric Asthma Controller Trial.. We compared the cost-effectiveness of low-dose fluticasone with that of montelukast in a randomized, controlled, multicenter clinical trial in children with mild-to-moderate persistent asthma. Analyses were also conducted on subgroups based on phenotypic factors. Effectiveness measures included (1) the number of asthma-control days, (2) the percentage of participants with an increase over baseline of FEV(1) of 12% or greater, and (3) the number of exacerbations avoided. Costs were analyzed from both a US health care payer's perspective and a societal perspective.. For all cost-effectiveness measures studied, fluticasone cost less and was more effective than montelukast. For example, fluticasone treatment cost $430 less in mean direct cost (P < .01) and resulted in 40 more asthma-control days (P < .01) during the 48-week study period. Considering sampling uncertainty, fluticasone cost less and was more effective at least 95% of the time. For the high exhaled nitric oxide (eNO) phenotypic subgroup (eNO ≥25 ppb) and more responsive PC(20) subgroup (PC(20) <2 mg/mL), fluticasone was cost-effective compared with montelukast for all cost-effectiveness measures, whereas not all the effectiveness measures were statistically different for the other 2 phenotypic subgroups.. For children with mild-to-moderate persistent asthma, low-dose fluticasone had lower cost and higher effectiveness compared with montelukast, especially in those with more airway inflammation, as indicated by increased levels of eNO and more responsivity to methacholine.

Topics: Acetates; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Cost-Benefit Analysis; Cyclopropanes; Female; Fluticasone; Humans; Male; Quinolines; Respiratory Function Tests; Sulfides

The effects of adding a second inhaled corticosteroid with a different particle size, compared with using an increased dose of a single inhaled corticosteroid, were assessed in patients with persistent asthma.. This was an open-label study of Japanese asthma patients over 20 years of age. After a 1-month run-in period, 36 patients with inadequate control while using salmeterol/fluticasone propionate 50/250 µg (SFC50/250) bd, were randomized to receive SFC50/500 bd or SFC50/250 plus mometasone 100 µg bd (SFC50/250/MF100) for 2 months.. Both treatments resulted in improvements in morning and evening PEF. There were no significant changes in FEV(1) , maximum mid-expiratory flow, maximum expiratory flow rate at 50%, maximum expiratory flow rate at 25% or exhaled NO (FENO) in the SFC50/500 group. On the other hand, there were significant improvements in FEV(1) % (+12.2%, P = 0.0142), %maximum mid-expiratory flow (+28.9%, P = 0.0181), %MEF50 (+32.4%, P = 0.0206) and %MEF25 (+30.3%, P = 0.0113) in the SFC50/250/MF100 group. The changes in FENO (-23.2% (P = 0.0157) in the SFC50/250/MF100 group and -14.5% (not significant) in the SFC50/500 group) did not differ significantly between the groups.. In patients with severe persistent asthma, addition of low-dose mometasone to SFC50/250 improved spirometric parameters, FENO and PEF, while an increase in dose from SFC50/250 to SFC50/ 500 only improved PEF.

Topics: Administration, Inhalation; Adult; Aged; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Japan; Male; Middle Aged; Mometasone Furoate; Nitric Oxide; Pregnadienediols; Respiratory Function Tests; Salmeterol Xinafoate; Severity of Illness Index; Spirometry; Treatment Outcome

To evaluate the impact of the School-Based Asthma Therapy trial on asthma symptoms among urban children with persistent asthma.. Randomized trial, with children stratified by smoke exposure in the home and randomized to a school-based care group or a usual care control group.. Rochester, New York.. Children aged 3 to 10 years with persistent asthma.. Directly observed administration of daily preventive asthma medications by school nurses (with dose adjustments according to National Heart, Lung, and Blood Institute Expert Panel guidelines) and a home-based environmental tobacco smoke reduction program for smoke-exposed children, using motivational interviewing.. Mean number of symptom-free days per 2 weeks during the peak winter season (November-February), assessed by blinded interviews.. We enrolled 530 children (74% participation rate). During the peak winter season, children receiving preventive medications through school had significantly more symptom-free days compared with children in the control group (adjusted difference = 0.92 days per 2 weeks; 95% confidence interval, 0.50-1.33) and also had fewer nighttime symptoms, less rescue medication use, and fewer days with limited activity (all P < .01). Children in the treatment group also were less likely than those in the control group to have an exacerbation requiring treatment with prednisone (12% vs 18%, respectively; relative risk = 0.64; 95% confidence interval, 0.41-1.00). Stratified analyses showed positive intervention effects even for children with smoke exposure (n = 285; mean symptom-free days per 2 weeks: 11.6 for children in the treatment group vs 10.9 for those in the control group; difference = 0.96 days per 2 weeks; 95% confidence interval, 0.39-1.52).. The School-Based Asthma Therapy intervention significantly improved symptoms among urban children with persistent asthma. This program could serve as a model for improved asthma care in urban communities.

Topics: Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Child, Preschool; Cotinine; Counseling; Directly Observed Therapy; Female; Fluticasone; Home Care Services; Humans; Indicators and Reagents; Inhalation Spacers; Linear Models; Male; New York; Saliva; Salmeterol Xinafoate; School Health Services; Seasons; Tobacco Smoke Pollution; Urban Population

Inhaled corticosteroids have become the first-line medication for treatment of childhood asthma. Possible adverse effects, such as those on bone metabolism and urinary excretion of calcium are in the focus of interest. We investigated the influence of inhaled fluticasone on bone metabolism and renal excretion of calcium, sodium, and potassium in asthmatic children.. Thirty asthmatic patients (mean age 12.24 ± 2.75 years) treated with 200-250 μg/day inhaled fluticasone were enrolled in the study. Prior to the initiation of therapy, as well as 12 weeks after following parameters were measured: serum sodium, potassium, calcium, phosphorus, creatinine, alkaline phosphatase, osteocalcin, intact parathyroid hormone levels, first-spot morning urine calcium/creatinine ratio, sodium/potassium ratio, and daily renal calcium excretion rate.. Serum electrolytes, alkaline phosphatase, parathyroid hormone, osteocalcin levels, as well as urinary calcium, sodium, and potassium excretion were within normal ranges. There was no statistical difference between values of those parameters prior and 12 weeks after initiation of the therapy.. Treatment with 200-250 μg/day inhaled fluticasone, in asthmatic children aged 9-16, during 12 weeks, did not affect serum osteocalcin level and renal excretion of calcium, sodium, and potassium.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Inflammatory Agents; Asthma; Bone and Bones; Calcium; Child; Female; Fluticasone; Humans; Male; Osteocalcin; Potassium; Prospective Studies; Sodium

The inhaled corticosteroid (ICS) fluticasone propionate (fluticasone) and the long-acting β2-agonist (LABA) formoterol fumarate (formoterol) are being made available as a combination product (fluticasone/formoterol, flutiform ®) in a single aerosol inhaler. This 12-week, open-label, randomized, active-controlled, parallel-group, multicentre, phase 3 study compared the efficacy and safety of fluticasone/formoterol with the commercially available combination product fluticasone/salmeterol.. Patients aged ≥ 18 years (N = 202) with mild-to-moderate-severe, persistent asthma for ≥ 6 months prior to screening were included in the study. After a screening phase (4-10 days), eligible patients were randomized 1:1 to receive fluticasone/formoterol or fluticasone/salmeterol during the 12-week treatment period. The primary objective was to demonstrate non-inferiority of fluticasone/formoterol versus fluticasone/salmeterol, measured by pre-dose forced expiratory volume in the first second (FEV1), at week 12.. Fluticasone/formoterol was comparable to fluticasone/salmeterol for the primary efficacy endpoint, mean pre-dose FEV1 at week 12. The new combination was also comparable to fluticasone/salmeterol for change from baseline to week 12 in pre-dose FEV1, change from pre-dose FEV1 at baseline to 2-hour post-dose FEV1 at week 12 and discontinuations due to lack of efficacy. Importantly, fluticasone/formoterol was superior to fluticasone/salmeterol in time to onset of action throughout the duration of the study. The two treatments demonstrated similar results for various other secondary efficacy parameters, including other lung function tests, patient-reported outcomes, rescue medication use, asthma exacerbations and Asthma Quality of Life Questionnaire scores. Fluticasone/formoterol was well tolerated and had a good safety profile that was similar to fluticasone/salmeterol.. The results of this study indicate that fluticasone/formoterol is as effective as fluticasone/salmeterol, and has a more rapid onset of action, reflecting the faster bronchodilatory effects of formoterol compared with those of salmeterol. If patients perceive the benefits of therapy with fluticasone/formoterol more rapidly than with fluticasone/salmeterol, this could have a positive impact on preference and adherence.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Male; Middle Aged; Quality of Life; Treatment Outcome; Young Adult

This report presents results of the first human study of a new dry powder inhaler (DPI-C). DPI-C uses reverse flow cyclone technology to retain larger particles in the device and to increase efficiency of respirable drug release. The study was conducted to determine comparative pharmacokinetics (not bioequivalence) of DPI-C and DPI-A (Advair Diskus®, GlaxoSmithKline) and to establish preliminary efficacy and safety of DPI-C.. Nineteen patients with mild-moderate asthma received two treatments (randomized crossover design). Treatments were one inhalation from DPI-A labeled to deliver 100 μg fluticasone propionate and 50 μg salmeterol, or one inhalation from DPI-C which contained ∼10% less of each drug per metered dose. Prior to dosing, 10 g of charcoal was administered. FEV1 increase over baseline (measured over 12 h), plasma concentrations of fluticasone and salmeterol (measured over 12.5 h), and occurrence of adverse events were the primary measures of device performance and safety.. Seventeen patients were evaluable. Response profiles of percent increase in FEV1 over baseline showed no statistically significant differences between devices. Peak plasma concentrations of both fluticasone (p=0.003) and salmeterol (p=0.084) were higher from DPI-C. Mean extent of absorption [area under the curve (AUC)] of fluticasone was approximately 30% greater with DPI-C, whereas AUC of salmeterol was approximately 40% greater with DPI-A.. DPI-C provided similar improvement in pulmonary function compared with DPI-A. Pharmacokinetic results showed a greater initial absorption of salmeterol with DPI-C but greater continued absorption and a 40% greater AUC with DPI-A, which we attribute to slower but more extensive oral absorption because of the greater mass of swallowed large particles of salmeterol generated by DPI-A. No patient reported any treatment-related adverse event or use of rescue medication during this study. Determination of the significance of the observed differences in pharmacokinetics from this single-dose study requires further exploration in studies using clinically relevant dosing regimens.

Topics: Adolescent; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Cross-Over Studies; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Salmeterol Xinafoate

The effect on linear growth of daily long-term inhaled corticosteroid therapy in preschool-aged children with recurrent wheezing is controversial.. We sought to determine the effect of daily inhaled corticosteroid given for 2 years on linear growth in preschool children with recurrent wheezing.. Children aged 2 and 3 years with recurrent wheezing and positive modified Asthma Predictive Index scores were randomized to a 2-year treatment period of chlorofluorocarbon-delivered fluticasone propionate (176 μg/d) or masked placebo delivered through a valved chamber with a mask and then followed for 2 years off study medication. Height growth determined by means of stadiometry was compared between treatment groups.. In the study cohort as a whole, the fluticasone group did not have significantly less linear growth than the placebo group (change in height from baseline difference, -0.2 cm; 95% CI, -1.1 to 0.6) 2 years after discontinuation of study treatment. In post hoc analyses children 2 years old who weighed less than 15 kg at enrollment and were treated with fluticasone had less linear growth compared with those treated with placebo (change in height from baseline difference, -1.6 cm; 95% CI, -2.8 to -0.4; P = .009).. Linear growth was not significantly different in high-risk preschool-aged children with recurrent wheezing treated with 176 μg/d chlorofluorocarbon-delivered fluticasone compared with placebo 2 years after fluticasone is discontinued. However, post hoc subgroup analyses revealed that children who are younger in age and of lesser weight relative to the entire study cohort had significantly less linear growth, possibly because of a higher relative fluticasone exposure.

Topics: Age Factors; Androstadienes; Anti-Asthmatic Agents; Asthma; Body Height; Body Weight; Child, Preschool; Cohort Studies; Double-Blind Method; Female; Fluticasone; Humans; Male; Respiratory Sounds

Although nocturnal awakenings help categorize asthma severity and control, their clinical significance has not been thoroughly studied.. We sought to determine the clinical consequences of nocturnal asthma symptoms requiring albuterol (NASRAs) in children with mild-to-moderate persistent asthma outside of periods when oral corticosteroids were used for worsening asthma symptoms.. Two hundred eighty-five children aged 6 to 14 years with mild-to-moderate persistent asthma were randomized to receive one of 3 controller regimens and completed daily symptom diaries for 48 weeks. Diary responses were analyzed for the frequency and consequences of NASRAs.. NASRAs occurred in 72.2% of participants at least once, and in 24.3% of participants, they occurred 13 or more times. The majority (81.3%) of nocturnal symptoms occurred outside of exacerbation periods and were associated the next day with the following events: albuterol use (56.9% of days preceded by nocturnal symptoms vs 18.1% of days not preceded by nocturnal symptoms; relative risk [RR], 2.3; 95% CI, 2.2-2.4), school absence (5.0% vs 0.3%; RR, 10.6; 95% CI, 7.8-14.4), and doctor contact (3.7% vs 0.2%; RR, 8.8; 95% CI, 6.1-12.5). Similar findings were noted during exacerbation periods (RRs of 1.7 for albuterol use, 5.5 for school absence, and 4.9 for doctor contacts). Nocturnal symptoms did not predict the onset of exacerbations.. Nocturnal symptoms requiring albuterol in children with mild-to-moderate persistent asthma receiving controller therapy occurred predominantly outside of exacerbation periods. Despite being poor predictors of exacerbations, they were associated with increases in albuterol use, school absences, and doctor contacts the day after nocturnal symptom occurrences.

Topics: Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Male; Prevalence; Sleep

Different strategies for disease control in real clinical practice are compared in terms of dynamics of functional parameters in patients with persistent bronchial asthma. This prospective multicentre surveillance study was carried out in 19 Russian clinics using the common protocol. The patients were divided in 3 groups in accordance with the changes of basal antiinflammatory therapy during the study period. Group A--stepwise increase in the extent of combined salmoterol/fluticason therapy, group B--long-term stable-dose salmoterol/fluticason therapy, group C--salmoterol/fluticason therapy with gradual decrease of the dose and/or transition to an alternative variant. Statistical analysis using Statistica 6.0 program included data from 543 patients. The results suggest that the two first modalities increased the level of control (ACT test) and improved characteristics of external respiration throughout the study period. Strategy 3 was associated with a decrease in the external respiration function and the level of control.

Topics: Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Salmeterol Xinafoate; Surveys and Questionnaires; Young Adult

Suplatast tosilate is a Th2 cytokine inhibitor that is effective for controlling persistent asthma. However, the long-term efficacy of suplatast is unknown. We compared the clinical efficacy of long-term monotherapy with suplatast tosilate with a low dose of inhaled steroids in patients with mild atopic asthma.. A total of 32 patients with mild atopic asthma were randomly assigned to receive suplatast (n=15) or fluticasone (n=17). In the suplatast group, 100 mg of suplatast was given orally 3 times a day (total daily dose = 300 mg) for 2 years. In the fluticasone group, 100 pg of fluticasone was inhaled twice a day (total daily dose = 200 tg) for 2 years.. In the suplatast group, the improvements in peak expiratory flow (PEF) rate and forced expiratory volume in 1 second (FEV1) and the changes in the symptom diary scale and frequency of beta2 stimulant inhalation were generally similar to those in the fluticasone group, and efficacy was maintained for 2 years. Improvements in inflammatory indices, such as the sputum eosinophil cationic protein (ECP) level and exhaled nitric oxide concentration, were comparable in the suplatast and fluticasone groups. The improvement in airway hyperresponsiveness was also similar in the 2 groups. The peripheral blood eosinophil percent change, serum ECP level, and total IgE antibody titer improved only in the suplatast group.. Long-term treatment with suplatast significantly improved symptoms and inflammatory indices in patients with mild atopic asthma. Along with fluticasone, suplatast is considered a useful drug for the management of mild atopic asthma.

Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Androstadienes; Arylsulfonates; Asthma; Disease Progression; Drug Dosage Calculations; Female; Fluticasone; Follow-Up Studies; Humans; Male; Middle Aged; Pilot Projects; Respiratory Function Tests; Sulfonium Compounds; Treatment Outcome

Measurement of short-term lower-leg growth rate in children by knemometry has become established as an integral part of the available measures of systemic activity of inhaled corticosteroids (ICS) in children. The aim of this study was to compare the effects of the novel ICS ciclesonide (CIC) and the ICS fluticasone propionate (FP) on lower-leg growth rate and hypothalamic-pituitary-adrenal-axis function in children with mild asthma. In a double-blind, placebo-controlled, three-period crossover study, 28 children, aged 6-12 yr, sequentially received daily doses of CIC 320 μg, FP 375 μg (330 μg ex-actuator) and placebo via a spacer in a randomized order. Each 2-wk treatment period was followed by a 2-wk washout period. Knemometry was performed at the beginning and end of each treatment period. Cortisol levels in 12-h overnight urine were measured at the end of each treatment period. No statistically significant differences were seen in lower-leg growth rates between CIC (0.30 mm/wk) and placebo (0.43 mm/wk) treatments. Lower-leg growth rate during FP treatment (0.08 mm/wk) was significantly reduced compared with both placebo [least squares (LS) mean: -0.35 (95% CI: -0.53, -0.18; p = 0.0002)] and CIC [LS mean: -0.23 (95% CI: -0.05, -0.40; p = 0.0137)]. Cortisol levels in 12-h overnight urine were significantly lower in the FP group when compared with CIC (p < 0.05); however, there were no statistically significant differences between each of the active treatments and placebo. CIC had no significant effect on lower-leg growth rate in children aged 6-12 yr with mild asthma. In contrast, a similar dose of FP significantly reduced lower-leg growth rate compared with placebo and CIC.

Topics: Androstadienes; Asthma; Child; Disease Progression; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Leg Bones; Male; Pituitary-Adrenal System; Pregnenediones; Time Factors

Long acting beta(2)-agonists (LABA) are widely used in children with asthma. Data from adults suggest that there is tachyphylaxis particularly to the bronchoprotective effects of LABA. There are no data in children. To determine whether LABA are subject to tachyphylaxis in school-aged children. Children were eligible for participation if they remained symptomatic on 400 microg of beclometasone dipropionate equivalent/day. Participants undertook a 4-wk run in period with open-label fluticasone 100 microg BD via Diskus. Children were then randomized to receive fluticasone 100 microg BD or salmeterol/fluticasone 50/100 microg BD via Diskus in a double-blind manner. Children underwent spirometry, cold air challenge and salbutamol reversibility testing at baseline, 4 and 8 wk. 37/42 children completed the study. There were significant improvements in basal FEV1 (% predicted) in the salmeterol/fluticasone group (n = 21) (+6.4% (95% CI: 2.4-10.5) p = 0.0033) but not in the fluticasone group (n = 16) [+1.2 (95% CI: -3.4 to 5.8) p = 0.5900]. There was a non-significant reduction in fall in FEV1 provoked by cold air in both groups. There was a significant lessening in the acute salbutamol response after 8 wk in the salmeterol/fluticasone group [-11.4% (95% CI: -17.6 to -5.2) p = 0.0010] but not in the fluticasone group [-1.6% (95% CI: -9.8 to 6.6) p = 0.6827]. Salmeterol/fluticasone therapy significantly improves basal FEV(1) in asthmatic children however, there is negligible additional bronchoprotection by week 4 of treatment and there is significant attenuation of salbutamol responsiveness when compared with fluticasone alone. Some of this reduction in salbutamol response may relate to the concurrent improvements in baseline lung function.

Topics: Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Salmeterol Xinafoate; Tachyphylaxis; Treatment Outcome

Treating allergic rhinitis may have a downstream anti-inflammatory effect on the lower airways. We conducted a dose ranging study in asthma and persistent allergic rhinitis to evaluate if intranasal corticosteroids exhibit a sparing effect on the dose of inhaled corticosteroid.. Twenty five participants were randomized to receive two weeks of 100 microg/day (Low dose) or 500 microg/day (High dose) of inhaled fluticasone propionate both with intranasal placebo; or inhaled fluticasone 100 microg/day with intranasal fluticasone 200 microg/day (Combined) in a double-blind cross-over fashion.. Low dose fluticasone produced a shift of 1.20 doubling-dilutions (95% CI, 0.63, 1.77); Combined fluticasone, 1.79 doubling-dilutions (95% CI, 0.77, 2.80) and high dose fluticasone, 2.01 doubling-dilutions (95% CI, 1.42, 2.61) in methacholine PC(20) from respective baselines. There was a significant difference between high and low doses: 0.82 doubling dilutions (95%CI, 0.12, 1.50) but not between combined and low dose 0.58 doubling dilutions (95% CI, -0.78, 1.95). Combined treatment alone produced improvements in peak nasal inspiratory flow (P < 0.001), rhinitis quality of life (P = 0.004) and nasal NO (P = 0.01); reduced blood eosinophil count (P = 0.03), and serum eosinophil cationic protein (P = 0.02). All treatments significantly improved tidal NO, FEV(1) and asthma quality of life.. High-dose fluticasone was superior to low dose fluticasone for methacholine PC20, demonstrating room for further improvement. Combined treatment was not significantly different from low dose fluticasone and we could not demonstrate a steroid sparing effect on methacholine PC20. Combined treatment alone produced improvements in upper airway outcomes and suppressed systemic inflammation but not adrenal function.

Topics: Administration, Inhalation; Administration, Intranasal; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Breath Tests; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Quality of Life; Respiratory Function Tests; Rhinitis, Allergic, Perennial; Young Adult

Retrospective pharmacogenetic studies have questioned whether patients with asthma who are arginine homozygous at the beta(2-)adrenergic receptor (position 16) should use long-acting beta-agonists.. To examine whether the response to salmeterol alone or in combination with an inhaled corticosteroid is influenced by beta- receptor polymorphisms.. Subjects using only as-needed albuterol were screened and completed two sequential open-label run-in periods (8 wk on as-needed albuterol; 8 wk on as-needed ipratropium). Five hundred forty-four subjects were randomized by Arg16Gly genotype to salmeterol alone or with fluticasone propionate for 16 weeks. Change from baseline in morning peak expiratory flow was the primary endpoint.. Lung function responses were sustained over treatment and no statistically significant changes from baseline between genotypes within treatments were observed. Overall mean changes in morning peak flow for salmeterol with fluticasone propionate were 32.6 L/min (Arg/Arg vs. Gly/Gly, 95% confidence interval [CI], -6.3, 22.1), 25.9 L/min (Arg/Arg vs. Arg/Gly, 95% CI, -7.1, 21.3), and 24.9 L/min (Arg/Gly vs. Gly/Gly, 95% CI, -13.0, 14.6), and for salmeterol alone were 19.4 L/min (Arg/Arg vs. Gly/Gly, 95% CI, -1.7, 21.4), 24.6 L/min (Arg/Arg vs. Arg/Gly, 95% CI, -13.0, 10.6), and 12.4 L/min (Arg/Gly vs. Gly/Gly, 95% CI, -0.2, 22.3) for Arg/Arg, Arg/Gly, and Gly/Gly genotypes, respectively. Other measures of asthma control showed similar responses.. The results showed no evidence of a pharmacogenetic effect of beta-receptor variation on salmeterol response. Clinical trial registered with www.clinicaltrials.gov (NCT 00102882).

Topics: Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Arginine; Asthma; Bronchodilator Agents; Child; Female; Fluticasone; Glycine; Humans; Male; Middle Aged; Pharmacogenetics; Polymorphism, Genetic; Prospective Studies; Receptors, Adrenergic, beta-2; Salmeterol Xinafoate; Young Adult

The role of combination ICS/LABA as initial controller therapy in mild, persistent asthma is uncertain. Therefore, the objective of this study was to compare the efficacy of initial controller therapy with fluticasone propionate (FP) 100 microg twice daily to the efficacy of fluticasone propionate/salmeterol xinafoate (FSC) 100/50 microg twice daily in patients with persistent asthma symptoms while using as-needed SABA alone.. This randomized, double-blind, parallel-group study was conducted at 45 general practice and 15 specialist centers. A total of 526 adult patients were randomized to receive FP or FSC for 24 weeks. The primary efficacy endpoint was change in morning peak expiratory flow (PEF) from baseline. Secondary efficacy endpoints included symptom- and rescue-free days; asthma exacerbation rate; asthma-related health-care utilization; and the onset of effect. Safety was assessed by monitoring adverse events.. Mean morning PEF was significantly greater in the FSC versus the FP group (P<0.001); this greater effect was evident as early as the first week of treatment (P<0.001). The percentages of symptom-free days and rescue-free days in the FSC group were 7.7% (P=0.009) and 8.4% (P=0.001) higher than the FP group, respectively. Trends toward lower exacerbation-related health care-utilization for FSC versus FP were not statistically significant and exacerbation rates were not significantly different. The incidence of adverse events was low with both treatments.. :Treatment with FSC was a more effective initial controller therapy than FP monotherapy in ICS-naïve patients who had uncontrolled asthma while using as-needed SABA alone.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Canada; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Salmeterol Xinafoate; Severity of Illness Index; Treatment Outcome; Young Adult

Currently available anti-inflammatory treatment for young children with asthma includes inhaled corticosteroids (ICS) and the leukotriene receptor antagonist (LTRA) montelukast.. To evaluate potential biomarkers of predicting short-term (6-week) response to ICS and LTRAs in children with asthma.. A total of 102 children aged 4 to 7 years with episodic asthma were enrolled in an open labelled single-centre study. Biomarkers and asthma characteristics were evaluated as predictors of treatment. Of 102 patients 45 became symptomatic during observation and were randomised to treatment either to montelukast or fluticasone for 6 weeks.. Forced Expiratory Volume in one second (FEV1) increased with both treatments: FEV1 at randomisation was 90.2% and after therapy 106.8% with fluticasone vs. 90.8% and 103.7% for montelukast, respectively, showing that montelukast and fluticasone were equally effective in this age group (p = 0.44). Strong correlations to a favourable treatment response were pre-bronchodilatory FEV1 (p < 0.001) and airway reversibility (p = 0.04) at time of randomisation. None of the other biomarkers (methacholine testing, exhaled nitric oxide [eNO], presence of allergy, total Immunoglobulin E [IgE], cumulative specific IgE, eosinophils and parental smoking) were predictive.. Despite the small sample size and the open-label design, the study suggests that the use of pre-bronchodilatory FEV1 and airway reversibility appears to be a good indicator of short-term anti-inflammatory therapy in young children with asthma.

Topics: Acetates; Algorithms; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Biomarkers, Pharmacological; Breath Tests; Child; Child, Preschool; Cyclopropanes; Female; Fluticasone; Humans; Male; Prognosis; Quinolines; Sulfides; Time Factors; Treatment Outcome

Inhaled corticosteroids (ICS) are the mainstay of asthma treatment, but conventional ICS may have limited effectiveness in inflammation and patency of small airways. Ciclesonide is delivered and deposited in the peripheral region of the lung as a small particle corticosteroid. The aim of the study is to compare the effects of ciclesonide with fluticasone propionate on small airway function in asthma.. Thirty mild persistent asthma patients treated with 200 microg of fluticasone propionate were randomized to receive either ciclesonide 200 microg once daily or fluticasone propionate 100 microg twice daily for 8 weeks. Small airway function was assessed by impulse oscillometry (IOS) and percentage of eosinophil induced sputum.. We observed that ciclesonide significantly improved IOS measured resistance of small airways (R5-R20; p<0.05), distal reactance (X5; p<0.01), reactance area (AX; p<0.01), and decreased late-phase sputum eosinophil level (p<0.01) compared with fluticasone propionate. There were no significant changes in spirometry indices in either group during the study.. These findings suggest that ciclesonide improves small airway function and inflammation compared with fluticasone propionate in mild asthma. This study provides evidence that IOS and late-phase induced sputum allows detection of changes in the small airways that can not be detected by spirometry.

Topics: Adult; Airway Resistance; Androstadienes; Asthma; Cell Count; Cell Movement; Eosinophils; Female; Fluticasone; Humans; Male; Middle Aged; Oscillometry; Pregnenediones; Spirometry; Sputum

Inhaled corticosteroids, such as fluticasone propionate (FP) and ciclesonide (CIC), are commonly used for the treatment of asthma. The objectives of this study were to characterize pharmacokinetics (PK) and pharmacodynamics (PD) of FP and a pharmacologically active metabolite of CIC (desisobutyryl-ciclesonide [Des-CIC]) using a nonlinear mixed-effects modeling approach, to investigate selected covariate effects on PK and PD parameters of FP and Des-CIC, and to assess the systemic effects of FP and CIC on serum cortisol suppression in patients with persistent asthma. This was a randomized, double-blind, placebo-controlled, double-dummy, 5-period, crossover, multicenter clinical study. A total of 32 patients were enrolled and given basic asthma medication (salmeterol 50 µg twice per day [BID] and CIC 160 µg daily in the evening) through the entire study. During crossover periods, patients were given placebo or CIC 160 µg BID (ex actuator), CIC 320 µg BID (ex actuator), FP 220 µg BID (ex actuator), or FP 440 µg BID (ex actuator). The FP and Des-CIC PK were described using a 1-compartment and a 2-compartment linear model with first-order absorption process. The FP population PK parameter estimates of the first-order rate constant, relative clearance, and volume of distribution were 4.07 1/h, 890 L/h, and 9800 L, respectively. The Des-CIC PK parameter estimates of the first-order absorption rate constant were 2.63 1/h, clearance 202 L/h (non-CIC treatment) or 271 L/h (CIC treatment), and volume of distribution 947 L. Gender was a significant covariate on the maximum cortisol release rate (male, 3440 µg/h; female, 4310 µg/h). The CIC showed the least serum cortisol suppression of the tested dosing regimens.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Anti-Allergic Agents; Area Under Curve; Asthma; Bronchodilator Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Half-Life; Humans; Hydrocortisone; Male; Middle Aged; Pregnenediones; Salmeterol Xinafoate; Sex Factors

Chronic rhinosinusitis associated with asthma is often difficult to treat effectively with intranasal corticosteroids alone. Thus, the aim of this study was to evaluate the effectiveness of combination treatment with an intranasal corticosteroid and a leukotriene-receptor antagonist (montelukast) in reducing the size of nasal polyps.. The subjects of this study were 20 patients with chronic rhinosinusitis associated with adult-onset asthma, which was being treated with inhaled corticosteroids. All patients were treated with intranasal fluticasone propionate, 200 microg/day, and montelukast, 10 mg/day, for 1 year. The size of nasal polyps and the score of sinus shadows were assessed with nasal endoscopy and computed tomography (CT), respectively, before and after treatment. The peripheral blood eosinophil counts were also evaluated before and after treatment.. Nasal polyps were significantly smaller after both 6 months (p<0.01) and 12 months of treatment (p<0.01) than before treatment. The decrease in the shadow score was statistically significant after both 6 months (p<0.01) and 12 months of treatment (p<0.01). Significant reductions in peripheral blood eosinophil counts were also seen after both 6 months (p<0.05) and 12 months of treatment (p<0.01). A significant correlation was found between the rate of change in the peripheral blood eosinophil count and that in the CT score after both 6 months (r=0.578, p=0.012) and 12 months (r=0.625, p=0.007).. Combined treatment with intranasal fluticasone propionate and montelukast, for at least 1 year, is effective for chronic rhinosinusitis associated with adult-onset asthma.

Topics: Acetates; Administration, Intranasal; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Anti-Allergic Agents; Asthma; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Eosinophils; Female; Fluticasone; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Quinolines; Rhinitis, Allergic, Perennial; Sinusitis; Sulfides; Tomography, X-Ray Computed; Treatment Outcome

This study investigates the impact of measuring adherence and providing feedback on medication usage by children with unstable asthma. Adherence was measured using an electronic monitoring device. Subjects were randomized to either being told of their adherence during review consultations or for their adherence to remain undisclosed to their parents and treating physician. Subjects were reviewed monthly for 4 months. Twenty-six children aged between 6 and 14 years were recruited. Adherence was significantly higher in the intervention group (79% versus 58%, p <.01). There were significant improvements in clinical measures of disease control compared with baseline in both groups. The change in forced expiratory volume in 1 s (FEV(1)) (% predicted) was greater in those subjects receiving feedback (13.8% versus 9.8%). However, lung function values were lower in the intervention group at baseline and the relative improvement failed to reach statistical significance. Measuring adherence and providing feedback increases the use of preventive medication. A larger study is required to explore implications for disease control.

Topics: Adolescent; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Combinations; Feedback, Psychological; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Medication Adherence; Patient Education as Topic; Treatment Outcome

For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking.. We randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 microg of fluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 microg of fluticasone twice daily (ICS step-up), 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily (LABA step-up), or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%.. A differential response occurred in 161 of 165 patients who were evaluated (P<0.001). The response to LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to 2.3; P=0.004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P=0.002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P=0.009). White race predicted a better response to LABA step-up, whereas black patients were least likely to have a best response to LTRA step-up (P=0.005).. Nearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy. (ClinicalTrials.gov number, NCT00395304.)

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Cross-Over Studies; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Eczema; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Leukotriene Antagonists; Logistic Models; Male; Prednisone; Quinolines; Salmeterol Xinafoate; Sulfides; Treatment Outcome

Cytokines and chemokines play important roles in asthma. However, little information exists on the effects of inhaled corticosteroids on cytokine and chemokine plasma levels in childhood asthma. We compared the pharmaceutical effects of two inhaled corticosteroids used in pediatric patients with mild-to-moderate asthma, budesonide and fluticasone propionate.. Pediatric patients aged 5-18 years old were enrolled in this randomized, open-label, observer-blinded study and received 3 months of treatment with either inhaled budesonide (200 microg/puff) or fluticasone propionate (250 microg/puff), at two puffs per day. Peak expiratory flow (PEF), exhaled nitric oxide, Asthma Control Test (ACT), plasma Levels of tumor necrosis factor-alpha, thymus and activation-regulated chemokine, and interferon-inducible protein 10 were measured before treatment and monthly for 3 months after treatment.. There were six patients in the budesonide group, and eight in the fluticasone group. After 3 months, both groups showed improved PEF. In the first month, PEF improved more in the budesonide group than in the fluticasone group, though the difference was not significant. After treatment, ACT scores in both groups were well controlled, except for one patient in the fluticasone group. The fluticasone group had a more significant reduction in exhaled nitric oxide than the budesonide group in the first month.. Improvements in lung function were more rapid in the budesonide group than the fluticasone group. However, patients in the fluticasone group had better anti-inflammatory responses than those in the budesonide group. We conclude that each inhaled corticosteroids have its own clinical and laboratory effects.

Topics: Adolescent; Androstadienes; Asthma; Breath Tests; Budesonide; Chemokine CCL17; Chemokine CXCL10; Child; Child, Preschool; Female; Fluticasone; Humans; Lung; Male; Nitric Oxide; Tumor Necrosis Factor-alpha

Patients with mild asthma may adapt to symptoms that may be neglected at a medical consultation. Despite active airway inflammation, indicating need for treatment symptoms may be poorly perceived and influence on quality of life. The aim was to find out if markers of asthma activity and quality of life are influenced by inhaled steroids in patients who regard themselves as free of symptoms.. Seventy steroid-free patients with mild asthma were treated with inhaled fluticasone (250 microg twice daily) or placebo for 3 months in a randomised, double-blind, study. Spirometry with reversibility test, exhaled nitric oxide (NO), bronchial responsiveness to methacholine and eucapnic dry air hyperventilation and quality of life [(Asthma Quality of Life Questionnaire (AQLQ)] were assessed before and after treatment.. Fluticasone, but not placebo, decreased methacholine responsiveness. Bronchial responsiveness to dry air and exhaled NO levels was significantly lowered by fluticasone compared with placebo. Quality-of-life scores were high already before treatment and were not significantly altered by treatment.. Treatment with an inhaled steroid in mild asthmatics altered bronchial responsiveness and exhaled NO levels but did not improve quality of life. In mild asthma, there is thus a space for improvement with regard to inflammatory parameters in patients who have only minor symptoms that are not influenced by treatment. In a long-term perspective, the indication for treatment of surrogate markers remains, however, unclear.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Biomarkers; Breath Tests; Bronchial Hyperreactivity; Female; Fluticasone; Humans; Inflammation; Male; Middle Aged; Nitric Oxide; Quality of Life; Severity of Illness Index; Spirometry

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Animals; Asthma; Eosinophils; Female; Fluticasone; Humans; Inflammation; Male; Middle Aged; Neutrophils; Prospective Studies; Sputum; Treatment Outcome

To compare the efficacy of ciclesonide (80 microg/day) with fluticasone propionate (200 microg/day) in mild to moderate persistent asthma.. Patients aged 12-75 years and previously treated with low doses of inhaled corticosteroid (fluticasone propionate 250 microg/day or equivalent) entered a 2-4 week run-in period during which only rescue medication was permitted. For inclusion into the double-blind, 24-week treatment period, patients had to show a forced expiratory volume in 1s (FEV(1)) of 61-90% predicted and a decrease in FEV(1) during run-in of >or=10%. Patients (n = 480) were randomized to ciclesonide 80 microg (ex-actuator) once daily in the evening or fluticasone propionate 100 microg (ex-valve) twice daily. The primary efficacy variable was the change from baseline in FEV(1). Secondary efficacy variables included asthma control and asthma-specific quality of life.. Both treatments significantly increased FEV(1) and other lung function variables from baseline (p < 0.0001, both groups, all variables). The least squares mean increases in FEV(1) were 0.46L (ciclesonide) and 0.52L (fluticasone propionate); non-inferiority of ciclesonide to fluticasone propionate was demonstrated (p = 0.0002, per-protocol analysis). Five patients in each group experienced asthma exacerbations. Improvements in the percent of days with asthma control (days with no asthma symptoms and no use of rescue medication) and asthma-specific quality of life were comparable between treatments.. The study confirmed similar efficacy of ciclesonide 80 microg once daily and fluticasone propionate 100 microg twice daily in mild to moderate persistent asthma. The low dose of ciclesonide was efficacious during long-term treatment. EudraCT number: 2004-001072-39.

Topics: Adolescent; Adult; Aged; Androstadienes; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Quality of Life; Respiratory Function Tests; Surveys and Questionnaires; Treatment Outcome; Young Adult

Inhaled corticosteroid (ICS)/long-acting beta(2)-agonist (LABA) combinations are the preferred maintenance therapy for adult asthma patients uncontrolled by ICS alone. Supporting data are largely from mixed populations of adolescents and adults, although ICS/LABA combinations are not approved for adolescents in all countries. This analysis evaluates overall asthma control in asthma patients aged >or=16 years receiving ICS/LABA combinations.. This was a post hoc analysis of asthma patients aged >or=16 years in a randomized, double-blind/open-label extension, parallel-group study. Patients received fixed maintenance-dose budesonide/formoterol (Symbicort Turbuhaler), fixed maintenance-dose salmeterol/fluticasone propionate (Seretide/Advair/Adoair Diskus) or adjustable maintenance-dose budesonide/formoterol. Patients used terbutaline or salbutamol for as-needed reliever medication. The primary efficacy variable was the odds of having a well controlled asthma week during the randomized treatment period.. ICS/LABA regimens were well tolerated and efficacious, and the odds for achieving a well controlled asthma week did not differ between groups in this sub-analysis. The number of exacerbations was similar between fixed-dose regimens; however, there were trends toward fewer exacerbations requiring hospitalization/emergency room treatment in the fixed- and adjustable maintenance-dose budesonide/formoterol groups (three and two events, respectively) than in the fixed-dose salmeterol/fluticasone propionate group (eight events). Improvements in forced expiratory volume in 1 second (FEV(1)) were small but significantly greater with fixed-dose budesonide/formoterol versus fixed-dose salmeterol/fluticasone propionate.. This post hoc analysis supports the use of ICS/LABA combinations in adults aged >or=16 years.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Salmeterol Xinafoate; Treatment Outcome; Young Adult

Small airways inflammation in asthma has been supposed to contribute to instability of the disease and therapy resistance. This study was designed to determine the validity of measurement of N(epsilon)-(carboxymethyl)lysine (CML) levels in induced sputum and alveolar concentrations of nitric oxide (NO) for the assessment of small airways inflammation in asthma.. The authors measured CML levels in induced sputum and the bronchial flux (Jno) and alveolar concentration (C(alv)) of NO in 37 asthmatic patients and 15 normal controls. After initial analysis, all asthmatics were randomly assigned to receive inhaled fluticasone propionate (FP; 400 microg/day, n = 21) or hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP; 400 microg/day, n = 16) for 12 weeks. And then the determination of exhaled NO level and sputum induction was performed after the treatment period.. CML levels in induced sputum were significantly higher in asthmatics than in normal controls (median [interquartile range], asthmatics: 53.0 [44.8-64.3] microg/ml, normal controls: 22.0 [14.8-28.3] microg/ml; p < .01). Similarly, Jno and C(alv) were also higher in asthmatics. Moreover, CML level was closely correlated with C(alv) but not with Jno in asthmatics (r = .47, p = .005). Jno was significantly correlated with forced expiratory volume in one second/forced vital capacity (FEV(1)/FVC), and CML level and C(alv) were correlated with forced expiratory flow between 25% and 75% of FVC (FEF(25-75)), an index of small airways obstruction. After FP treatment, the decrease in CML level and Calv were very small. In contrast, these levels were markedly decreased after HFA-BDP treatment. Moreover, even after FP or HFA-BDP treatment, CML level was significantly correlated with C(alv).. This novel, noninvasive technique of measurement of CML levels in induced sputum and C(alv) may prove to be important not only in the evaluation of small airways inflammation but also in helping us move toward a better understanding of the roles of the small airways in the pathogenesis of asthma.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biomarkers; Bronchi; Female; Fluticasone; Humans; Inflammation; Lysine; Male; Middle Aged; Nitric Oxide; Pulmonary Alveoli; Reproducibility of Results; Sputum

Single-dose inhaled corticosteroids (ICS) induce direct anti-inflammatory effects in asthma thereby improving airway hyperresponsiveness (AHR). A novel enhanced-affinity ICS, fluticasone furoate (FF), demonstrated a prolonged duration of action in vitro. The aim of this study was to evaluate the efficacy and duration of action of a single dose of FF by studying protection against AHR to adenosine 5'-monophosphate (AMP) and effects on exhaled nitric oxide (eNO).. A randomized, double-blind, placebo-controlled, 6-way crossover study (FFA10026) was performed in 24 patients with allergic asthma (mean age 32.8 years, FEV(1) ≥ 70% predicted and PC(20) AMP ≤ 50 mg/ml). Each subject received a single dose of FF 1000 μg, fluticasone proprionate (FP) 1000 μg, or placebo at 2 (FF only), 14 or 26 h prior to AMP challenge and eNO measurement.. FF significantly improved PC(20) AMP compared to placebo, the difference in doubling concentrations being 2.18 (95% confidence interval: 1.13-3.23), 1.54 (0.48-2.59), and 1.30 (0.26-2.34) at 2, 14 and 26 h. FP improved PC(20) AMP significantly at 14 h compared to placebo, but not at the 26-hour time point, the difference in doubling concentrations being 1.72 (0.70-2.75) and 0.33 (-0.69-1.34). There was no significant effect on eNO after either FF or FP at all time points. FF was well tolerated and there were no serious adverse events.. The new inhaled corticosteroid FF, but not FP, demonstrates prolonged protection up to 26 h against AHR to AMP in asthma patients.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Exhalation; Female; Fluticasone; Humans; Hypersensitivity; Male; Nitric Oxide; Respiratory Function Tests

To evaluate the effect of montelukast, 5 mg, or inhaled salmeterol, 50 microg, added to inhaled fluticasone in reducing the maximum percentage decrease in forced expiratory volume in 1 second (FEV1) after a standardized exercise challenge and response to rescue bronchodilation with albuterol in children aged 6 to 14 years with persistent asthma and exercise-induced bronchoconstriction (EIB).. Randomized, double-blind, double-dummy, multicenter, 2-period, 4-week, crossover study conducted between December 22, 2005 and November 14, 2008 at 30 centers in Europe, Asia, Mexico, and South America. Patients with asthma receiving inhaled corticosteroids demonstrated an FEV1 of 70% or higher of the predicted value and EIB (defined as a decrease in FEV1 > or = 15% compared with preexercise baseline FEV1 on 2 occasions before randomization). Standardized exercise challenges were performed at baseline (prerandomization) and at the end of each active treatment period.. Of 154 patients randomized, 145 completed the study. Montelukast, compared with salmeterol, significantly reduced the mean maximum percentage decrease in FEV1 (10.6% vs 13.8%; P = .009), mean area under the curve for the first 20 minutes after exercise (116.0% x min vs 168.8% x min; P = .006), and median time to recovery (6.0 vs 11.1 minutes; P = .04). Response to albuterol rescue after exercise challenge was significantly greater (P < .001) with montelukast. Montelukast and salmeterol were generally well tolerated.. Attenuation and response of EIB to albuterol rescue after exercise challenge were significantly better with montelukast than with salmeterol after 4 weeks of treatment.

Topics: Acetates; Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchoconstriction; Child; Cross-Sectional Studies; Cyclopropanes; Double-Blind Method; Exercise; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Quinolines; Salmeterol Xinafoate; Sulfides

Patient-reported outcomes provide new insights into the dynamics of asthma management. Further to asthma control and quality of life, self-reported side effects of treatment can be assessed with the validated Inhaled Corticosteroid Questionnaire (ICQ).. To compare patient-reported side effects between the inhaled corticosteroids ciclesonide and fluticasone propionate.. Patients with moderate or moderate-to-severe asthma, pre-treated with a constant dose and type of medication, were randomized in three separate studies: 1) once daily ciclesonide 320 μg (n = 234) or twice daily fluticasone propionate 200 μg (n = 240); 2) twice daily ciclesonide 320 μg (n = 255) or twice daily fluticasone propionate 375 μg (n = 273); and 3) twice daily ciclesonide 320 μg (n = 259) or twice daily fluticasone propionate 500 μg (n = 244). Patients rated the side effect questions of the 15 domain ICQ on a 7-point Likert scale (0 = not at all, 6 = a very great deal) during scheduled visits.. The majority of side effect scores remained similar with ciclesonide but worsened statistically significantly with fluticasone propionate from baseline to the end of the study in within-treatment analyses. In between-treatment analyses of studies 1 and 3 ciclesonide significantly improved total side effect scores (p < 0.025) and 14 out of 30 individual local and systemic domain scores (p < 0.025) compared with fluticasone propionate. In Study 2, although ciclesonide improved the majority of scores compared with fluticasone propionate only 'oropharyngeal itching' reached statistical significance (p < 0.025, one-sided).. Patient-perceived side effects differ depending on the type of inhaled corticosteroids used. Patients with moderate-to-severe asthma report less intense side effects assessed with ICQ with ciclesonide than with fluticasone propionate.. The reported trials were completed before July 1 2005 and, therefore, are not registered.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchoconstrictor Agents; Child; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Young Adult

For children with symptomatic asthma despite low to moderate doses of inhaled corticosteroids, evidence is still lacking whether to add a long-acting bronchodilator or to increase the dose of inhaled corticosteroids.. To evaluate whether salmeterol/fluticasone propionate (SFP), 50/100 μg twice a day, is noninferior regarding symptom control compared with fluticasone propionate (FP), 200 μg twice a day Diskus in children with symptomatic asthma.. A multicenter, randomized, parallel-group, double-blind study was performed comparing SFP and FP treatment during 26 weeks on asthma control and lung function.. A total of 158 children, 6-16 years old, still symptomatic on FP, 100 μg twice a day, during a 4-week run-in period, were included. Percentage of symptom-free days during the last 10 weeks of the treatment period did not differ between treatment groups (per protocol analysis: adjusted mean difference [FP minus SFP] 2.6%; 95% confidence interval, -8.1 to 13.4). Both groups showed substantial improvements of about 25 percent points in symptom-free days (both P < 0.001 from baseline). Lung function measurements (FEV(1), FVC, PEF rate, and maximal expiratory flow) did not differ between groups except for a slight advantage in maximal expiratory flow in the SFP group at 1 week. No differences were found between FP and SFP regarding exacerbation rates, adverse events, or growth.. In our study the efficacy on symptom control and lung function of the combination of a long-acting bronchodilator with inhaled corticosteroid is equal to doubling the dose of the inhaled corticosteroid in children still symptomatic on a moderate dose of inhaled corticosteroid.

Topics: Administration, Inhalation; Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Respiratory Function Tests; Salmeterol Xinafoate

Asthma control is now recognized as the main goal of asthma therapy. Guidelines recommend finding the lowest effective dose of inhaled corticosteroids in children with persistent asthma.. The aim of this study was to investigate the efficacy of an allergen-specific immunotherapy with a high-dose hypoallergenic mite preparation (allergoid) as steroid-sparing agent in children with allergic asthma.. Sixty-five children with asthma (Global Initiative for Asthma treatment levels II and III; 6-17 years old), after reaching asthma control with inhaled steroids during a 5-month baseline period, were randomized for subcutaneous mite allergoid immunotherapy (SCIT) plus fluticasone propionate (FP) or FP therapy alone for 2 years. During 2 subsequent 5-month winter periods, steroid therapy was adjusted according to predefined dose steps, determining and comparing the changes in FP dosages and the lowest FP dose sufficient to maintain asthma control. Immunologic and functional investigations were also carried out.. Children treated with house dust mite SCIT plus FP were able to significantly reduce the FP dose by more steps (P < .05), compared with the control group on FP alone. The mean daily dose in the immunotherapy group decreased from 330.3 μg in the baseline period to 151.5 μg after 2 treatment years, whereas in the control group the dose decreased from 290.6 μg to 206.3 μg. Compared with the control group, significant improvement was also observed in morning peak expiratory flow (P = .0315). Significantly increased levels of specific IgG(1) (P = .0001) and IgG(4) (P < .0001) were also observed.. Adding a mite allergoid SCIT to pharmacologic treatment is an effective and safe strategy to reduce corticosteroid doses while maintaining disease control in children with mite-induced allergic asthma.

Topics: Administration, Inhalation; Administration, Sublingual; Adolescent; Allergens; Androstadienes; Animals; Anti-Allergic Agents; Asthma; Child; Desensitization, Immunologic; Female; Fluticasone; Humans; Male; Pyroglyphidae; Respiratory Function Tests

Airway inflammation is a key pathological feature of asthma which underlies its clinical presentation.. To examine whether adding a leukotriene modifier to an inhaled corticosteroid produces further clinical and/or anti-inflammatory benefits in patients symptomatic on short-acting beta(2)-agonists.. Patients uncontrolled on short-acting beta(2)-agonists were treated for 12 weeks with either fluticasone propionate (100mcg BD) or fluticasone propionate (100mcg BD) and montelukast (10mg QD) in a randomized, double-blind, parallel group study. Bronchoscopy with endobronchial biopsy and bronchoalveolar lavage (BAL) was performed before and after treatment to compare effects on airway inflammation.. Of 103 subjects enrolled, 89 subjects completed treatment and 82 subjects had matched pair biopsy samples. Submucosal eosinophil counts, the primary endpoint, and asthma control improved to similar extents after both treatments (p

Topics: Acetates; Administration, Inhalation; Adult; Androstadienes; Asthma; Bronchi; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Eosinophilia; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Quinolines; Sulfides; Treatment Outcome

Statins have anti-inflammatory actions which in theory are potentially beneficial in asthma. Small trials have failed to show a significant benefit, but a systematic study to evaluate the steroid-sparing effect of statin treatment has not been carried out.. A randomised, placebo-controlled, crossover trial was conducted of simvastatin 40 mg at night with simultaneous stepwise reduction of fluticasone propionate dose until loss of control occurred, followed by an increase until regain of control ('minimum' dose required) in 51 patients with asthma and sputum eosinophils (steroid-free) ≥ 2%.. 43 patients completed the study. There was no significant difference in 'minimum' inhaled corticosteroid (ICS) dose requirement between simvastatin and placebo: (median (IQR) 50 μg daily (0-250) vs 100 μg daily (0-250), p=0.931). 'Minimum' dose distribution was similar (p=0.269). The fluticasone dose at which loss of control occurred did not differ significantly between simvastatin and placebo (p=0.404). In patients with loss of control in both treatment arms, fluticasone dose at loss of control was similar with simvastatin and placebo (median (IQR) 50 μg daily (0-100) for both, p=0.620). In those patients who reached 0 μg/day (n=18), Astma Control Questionnaire (ACQ) was lower (p=0.037), forced expiratory volume in 1 s (FEV(1)) higher (p<0.01) and sputum eosinophils lower with simvastatin compared with placebo (9.5% compared with 25.4%, p=0.033).. Simvastatin does not have clinically important steroid-sparing effects in patients with eosinophilic asthma. In the absence of steroid, simvastatin is associated with minor improvements in symptoms and lung function, and a reduction in sputum eosinophils. Clinical trial number ACTRN12606000531516.

Topics: Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epidemiologic Methods; Female; Fluticasone; Glucocorticoids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Simvastatin; Young Adult

PCR studies have demonstrated evidence of Mycoplasma pneumoniae and Chlamydophila pneumoniae in the lower airways of patients with asthma.. To test the hypothesis that clarithromycin would improve asthma control in individuals with mild-to-moderate persistent asthma that was not well controlled despite treatment with low-dose inhaled corticosteroids.. Adults with an Asthma Control Questionnaire score ≥1.5 after a 4-week period of treatment with fluticasone propionate were entered into a PCR-stratified randomized, controlled trial to evaluate the effect of 16 weeks of either clarithromycin or placebo, added to fluticasone, on asthma control in individuals with or without lower airway PCR evidence of M pneumoniae or C pneumoniae.. A total of 92 participants were randomized. Twelve (13%) subjects demonstrated PCR evidence of M pneumoniae or C pneumoniae in endobronchial biopsies; 80 were PCR-negative for both organisms. In PCR-positive participants, clarithromycin yielded a 0.4 ± 0.4 unit improvement in the Asthma Control Questionnaire score, with a 0.1 ± 0.3 unit improvement in those allocated to placebo. This between-group difference of 0.3 ± 0.5 (P = .6) was neither clinically nor statistically significant. In PCR-negative participants, a nonsignificant between-group difference of 0.2 ± 0.2 units (P = .3) was observed. Clarithromycin did not improve lung function or airway inflammation but did improve airway hyperresponsiveness, increasing the methacholine PC(20) by 1.2 ± 0.5 doubling doses (P = .02) in the study population.. Adding clarithromycin to fluticasone in adults with mild-to-moderate persistent asthma that was suboptimally controlled by low-dose inhaled corticosteroids alone did not further improve asthma control. Although there was an improvement in airway hyperresponsiveness with clarithromycin, this benefit was not accompanied by improvements in other secondary outcomes.

Topics: Adult; Androstadienes; Anti-Bacterial Agents; Anti-Inflammatory Agents; Asthma; Chlamydophila pneumoniae; Clarithromycin; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Mycoplasma pneumoniae; Polymerase Chain Reaction; Surveys and Questionnaires; Treatment Outcome

The aim was to investigate the health impact of nasal polyposis with asthma and to study effects of endoscopic sinus surgery (ESS), and addition of fluticasone propionate nasal drops (FPND), on health related quality of life (HRQoL).. Prospective study of 68 patients with nasal polyposis and asthma. Effects were measured with Study 36-Item Short Form (SF-36). A randomized, double-blind, placebo-controlled 14-weeks phase measuring additive effects of FPND 400 µg twice daily (b.i.d.) was included.. HRQoL was significantly decreased in both Physical Component Summary, PCS, (45 vs 48, p=0.049) and Mental Component Summary, MCS, (43 vs 51, p<0.001) vs reference population. ESS significantly improved PCS, (p=0.027) and MCS (p=0.021) after five weeks. We found significant additional benefit of FPND on three domains (RP, p=0.002; VT, p=0.007; SF, p=0.002). The increase in HRQoL with FPND reached reference population levels in all domains, as well as in both PCS (50, p=0.003) and MCS (52, p=0.002), five weeks after ESS.. FPND 400 µg b.i.d. can be added to ESS in order to improve, and to reach population levels of, HRQoL already five weeks post-ESS. Physicians should evaluate HRQoL and consider ESS with nasal steroids early in their treatment of these patients.

Topics: Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Comorbidity; Double-Blind Method; Endoscopy; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps; Quality of Life

Inhaled corticosteroid therapy suppresses nitric oxide levels (NO) of airway origin but not necessarily NO of alveolar or small airway origin. Systemic therapy with an oral anti-leukotriene agent may suppress NO production in distal airways and alveoli not reached by inhaled therapy.. Adult patients with mild asthma were treated for 3 weeks with inhaled fluticasone 250 microg twice daily then with inhaled fluticasone plus oral montelukast 10 mg daily for 3 additional weeks. We monitored exhaled NO (eNO), spirometry, lung volumes, and asthma symptoms scores at baseline and at the end of each treatment period. In a subset of patients, we continued with montelukast monotherapy and repeated these measurements.. In the 18 patients studied, pulmonary function parameters and asthma symptom scores were not altered significantly from baseline by any therapy. The total eNO at baseline was 55+/-35.3 ppb, dropping to 28.1+/-15.3 ppb (p=0.005) after 3 weeks of fluticasone and to 23.5+/-14 ppb (p=0.001 vs. baseline) after the addition of montelukast. The trend towards reduced total eNO with the combination therapy vs. monotherapy was not statistically significant. Alveolar eNO dropped from 4.2+/-2.4 at baseline to 3.0+/-1.5 (p=0.1) after fluticasone and then to 2.2+/-0.9 (p=0.08 vs. baseline) after fluticasone plus montelukast, increasing then to 3.8+/-1.8 after montelukast alone (p=0.6 vs. baseline).. Leukotriene receptor antagonists administered systemically might decrease small airway/alveolar sites of inflammation when combined to inhaled corticosteroid therapy.

Topics: Acetates; Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchi; Cyclopropanes; Female; Fluticasone; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Nitric Oxide; Prospective Studies; Quinolines; Sulfides

This was a 3-year "real-life" study, during which patients' medication was increased and decreased to achieve sustained asthma control. Patients (282) were randomised to receive treatment with SAL 50microg, FP 250microg, or SFC 50/250microg via a Diskustrade mark inhaler, bid. A 12-month double-blind period was followed by a 2-year open phase. The physician increased or decreased patients' medication to achieve and maintain asthma control at regular clinical assessments using criteria based on the asthma treatment guidelines. On completion 73% (168/229) of the subjects were receiving SFC to maintain control of their asthma, compared with 21% (49/229) receiving FP and 5% (12/229) receiving SAL. Odds ratio for requiring increased treatment were 2.66 (p=0.002) for patients initially randomised to FP and 9.38 (p<0.0001) SAL, compared with SFC. Time until 25% of patients first required an increase in study medication was 6months for patients initially treated with SAL compared to 12months for FP and 21months for SFC. Symptoms and use of rescue medication improved first, followed rapidly by PEF with the greatest improvements occurring over the first year. Airway hyperresponsiveness continued to improve throughout the study. The majority of patients achieved and maintained control of asthma over a 3-year period with physician-driven medication changes. Patients treated with SFC were more likely to achieve control than patients treated with FP or SAL alone. Continuing improvements in airway hyperresponsiveness indicate the importance of maintaining treatment after clinical control of symptoms and lung function are achieved.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Family Practice; Female; Fluticasone; Follow-Up Studies; Forced Expiratory Volume; Humans; Logistic Models; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Salmeterol Xinafoate; Treatment Outcome; Young Adult

Determination of the benefits and limitations of specific physiologic tests has not been well studied in long-term clinical pediatric trials.. We sought to determine the utility of impulse oscillometry in a long-term comparison of 3 controller regimens in children with persistent asthma.. Children 6 to 14 years of age with mild-to-moderate persistent asthma were characterized with oscillometry and spirometry before entry into a clinical trial and then serially during 48 weeks of therapy with either an inhaled corticosteroid, a combination inhaled corticosteroid with a long-acting beta-agonist, or a leukotriene receptor antagonist.. The FEV(1)/forced vital capacity ratio, as well as the forced expiratory flow from 25% to 75% of forced vital capacity in terms of spirometric parameters and the reactance area (XA) from impulse oscillometry, appeared to complement information provided by FEV(1) when comparing the tests and factors that appeared to predict a response to treatment. XA was unique in that it, as distinct from spirometric variables, reflected ongoing improvement during the latter part of the trial. In general, improvements in XA during the latter part of the study occurred independently of indices of atopy and the level of airway responsiveness.. Assessment of respiratory mechanics over time with oscillometry might offer additional insights into the response of asthmatic patients to therapy. In particular, the pattern of improvement seen in XA over the course of therapy suggests this test might detect alterations in airway mechanics not reflected by spirometry. The possibility that changes in XA reflect ongoing improvement in small airway function deserves additional study.

Topics: Acetates; Adolescent; Albuterol; Androstadienes; Asthma; Biomarkers; Child; Cyclopropanes; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Oscillometry; Quinolines; Salmeterol Xinafoate; Spirometry; Sulfides; Vital Capacity

Ciclesonide is a new inhaled corticosteroid (ICS). Information about its clinical efficacy and safety in relation to other ICS in children is needed for clinical positioning.. This 12-week, randomized, double-blind, double-dummy, three-arm, parallel-group study compared the efficacy and safety of ciclesonide with fluticasone propionate in children with mainly moderate and severe persistent asthma.. Seven hundred and forty-four patients (aged 6-11 years) were randomized to ciclesonide (80 or 160 microg once daily) or fluticasone propionate (88 microg twice daily), following a 2-4-week run-in. Efficacy measurements included forced expiratory flow in 1s (FEV(1)), morning peak expiratory flow (PEF), asthma symptom scores, rescue medication use and quality of life. Systemic effect was assessed by 24-hour urine free cortisol adjusted for creatinine.. FEV(1) and morning PEF increased from baseline in all groups (p<0.0001). Ciclesonide 160 microg was not inferior to fluticasone propionate 176 microg for FEV(1) (p=0.0030, one-sided). In all groups, asthma symptom score sums and rescue medication use significantly improved (p<0.0001). The percentages of asthma symptom-, rescue medication- and nocturnal awakening-free days were high, with no significant differences between treatments. Quality of life scores improved with all treatments (p<0.0001). A significant dose-response occurred between low and higher doses of ciclesonide for exacerbations and asthma control definitions. The incidences of adverse events were comparable across treatments. Urine free cortisol levels decreased significantly with fluticasone propionate (p=0.0103), but not with ciclesonide.. Once-daily ciclesonide has a clinical effect similar to that of fluticasone propionate, but does not suppress cortisol excretion, in children with moderate and severe asthma.

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchoconstrictor Agents; Child; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Lung; Male; Methacholine Chloride; Pregnenediones; Quality of Life; Treatment Outcome

Although virus-induced wheezing is common in preschool-age children, optimal management remains elusive. We examined the efficacy and safety of preemptive treatment with high-dose fluticasone in reducing the severity of recurrent virus-induced wheezing in children.. We randomly assigned 129 children who were 1 to 6 years of age to receive 750 microg of fluticasone propionate (ex-valve [manufacturer-measured] dose) or placebo twice daily, beginning at the onset of an upper respiratory tract infection and continuing for a maximum of 10 days, over a period of 6 to 12 months. The primary outcome was rescue oral corticosteroid use. Secondary outcomes included symptoms, use of beta(2)-agonists, acute care visits, hospitalizations, discontinuation of the study drug, change in growth and bone mineral density, basal cortisol level, and adverse events.. Over a median period of 40 weeks, 8% of upper respiratory tract infections in the fluticasone group led to treatment with rescue systemic corticosteroids, as compared with 18% in the placebo group (odds ratio, 0.49; 95% confidence interval [CI], 0.30 to 0.83). Children who were treated with fluticasone, as compared with those who were given placebo, had smaller mean (+/-SD) gains from baseline in height (6.23+/-2.62 cm [unadjusted value]; z score, -0.19 +/-0.42 vs. 6.56+/-2.90 cm [unadjusted value]; z score, 0.00+/-0.48; difference between groups in z score from baseline to end point, -0.24 [95% CI, -0.40 to -0.08]) and in weight (1.53+/-1.17 kg [unadjusted value]; z score, -0.15+/-0.48 vs. 2.17+/-1.79 kg [unadjusted value]; z score, 0.11+/-0.43; difference between groups in z score from baseline to end point, -0.26 [95% CI, -0.41 to -0.09]). There were no significant differences between the groups in basal cortisol level, bone mineral density, or adverse events.. In preschool-age children with moderate-to-severe virus-induced wheezing, preemptive treatment with high-dose fluticasone as compared with placebo reduced the use of rescue oral corticosteroids. Treatment with fluticasone was associated with a smaller gain in height and weight. Given the potential for overuse, this preventive approach should not be adopted in clinical practice until long-term adverse effects are clarified. (ClinicalTrials.gov number, NCT00238927.)

Topics: Administration, Inhalation; Androstadienes; Asthma; Bronchodilator Agents; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Growth; Humans; Infant; Male; Respiratory Sounds; Respiratory Tract Infections; Virus Diseases

We compared the systemic and clinical effects of ciclesonide (CIC) and fluticasone propionate (FP) administered, in addition to CIC 160 microg x day(-1) and salmeterol 50 microg twice daily, in 32 patients with persistent asthma using a randomised double-blind, placebo-controlled, double-dummy, five-period crossover design. All patients exhibited a provocative concentration leading to a 20% decrease in forced expiratory volume in 1 s (PC(20)) methacholine <8 mg x mL(-1) and a PC(20) adenosine <60 mg x mL(-1). Primary outcome was 24-h serum cortisol suppression after 7 days. Secondary outcomes were changes in PC(20) methacholine and adenosine after 9 days. FP 500 microg x day(-1) and 1,000 microg x day(-1) significantly suppressed cortisol secretion versus placebo by -46.2 (95% confidence interval (CI) -83.8- -8.5) nmol x L(-1) and by -76.1 (95% CI -112.9- -39.3) nmol x L(-1), respectively. Neither dose of CIC (320 nor 640 microg x day(-1)) had a significant suppressive effect (-28.2 (95% CI -65.5-9.2) nmol x L(-1) and -37.3 (95% CI -74.7-0.0) nmol x L(-1), respectively). Differences between FP 1,000 microg x day(-1) and both CIC treatments were statistically significant (CIC 320 microg x day(-1): -48.0 (95% CI -84.8- -11.1) nmol x L(-1); CIC 640 microg x day(-1): -38.8 (95% CI -75.7- -1.9) nmol x L(-1)). Compared with placebo, the increase in PC(20) adenosine after the four treatments was small, but significant. Greater improvements in PC(20) adenosine were seen with FP 500 microg x day(-1) (1.8 (95% CI 1.0-2.6) doubling concentrations) compared with CIC 320 microg x day(-1) (0.9 (95% CI 0.1-1.7) doubling concentrations). No significant difference was seen between CIC 640 microg x day(-1) and FP 1,000 microg x day(-1). For a similar decrease in hyperresponsiveness, cortisol secretion was suppressed significantly with moderate-to-high doses of fluticasone propionate, but not with ciclesonide.

Topics: Adenosine; Adolescent; Adult; Aged; Albuterol; Analysis of Variance; Androstadienes; Anti-Allergic Agents; Area Under Curve; Asthma; Bronchial Provocation Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Least-Squares Analysis; Male; Methacholine Chloride; Middle Aged; Placebos; Pregnenediones; Salmeterol Xinafoate; Spirometry; Treatment Outcome

Nasal polyposis is a disease known to be associated with asthma. The management is anti-inflammatory, with topical and oral corticosteroids as the first-line treatment. The effect of surgical treatment on lower airway inflammation has not been sufficiently studied.. The aim of this study is to investigate the effects of functional endoscopic sinus surgery (FESS) as well as fluticasone proprionate nasal drops (FPND) 400 microg b.i.d. on nasal and lower airway parameters in asthmatics with nasal polyposis.. This was a prospective 21-week study of 68 patients with asthma and nasal polyposis, on the benefits of FESS on nasal '(butanol test, subjective olfaction, peak nasal inspiratory flow, congestion, rhinorrhoea, and polyp score)', and on the lower airway parameters (dyspnea, cough, mean daily peak expiratory flow rate (PEFR), and lung function tests). It also included a randomized, double-blind, placebo-controlled 14 weeks phase on FPND.. Functional endoscopic sinus surgery significantly improved mean asthma symptom scores and daily PEFR and all nasal parameters including subjective and objective olfaction tests. This is the first study that shows the benefits of FESS on butanol tests in patients with nasal polyposis. We found no significant difference between topical treatment with FPND or placebo in the nasal or lower airway variables.. Functional endoscopic sinus surgery improved nasal and asthma symptoms in patients with nasal polyposis. Functional endoscopic sinus surgery could be considered early in the natural course of nasal polyposis with concomitant asthma, as well as a second-line treatment in nasal polyposis patients with a reduced sense of smell. The potential benefits of FPND 400 microg b.i.d. were probably overshadowed by FESS.

Topics: Adult; Aged; Androstadienes; Anti-Allergic Agents; Asthma; Double-Blind Method; Endoscopy; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Polyps; Olfaction Disorders; Paranasal Sinuses; Peak Expiratory Flow Rate; Prospective Studies; Smell

To evaluate the efficacy of add-on montelukast on asthma control and allergic rhinitis symptoms in asthmatic patients still symptomatic with chronic treatment with inhaled corticosteroid and long-acting beta(2) agonist (ICS/LABA), irrespective of the dose.. This 2-month, open-label, real-life, multicentre, observational study was undertaken by 499 general practitioners in Belgium. Patients (>or= 4 years old) with uncontrolled asthma despite fluticasone/salmeterol or budesonide/formoterol therapy had oral montelukast 4, 5, or 10 mg daily added to their therapy, depending on the registered dose for their age. Asthma control, assessed by the 6-item Juniper Asthma Control Questionnaire (ACQ) was recorded at baseline and after 2 months of treatment with montelukast and the patients' global evaluation of asthma was also recorded at the end of the study. Concomitant allergic rhinitis symptoms were evaluated according to the patients' perception.. A total of 5769 patients were eligible for analysis. Addition of montelukast was associated with significant decrease in mean (SD) ACQ score (from 1.97 [0.77] at baseline to 1.05 [0.69] after add-on treatment, p < 0.001). There was also a significant improvement in all individual symptoms of the ACQ score (p < 0.001). After 2 months, 89% of the patients reported global improvement of their asthma, with a good correlation between patients' global evaluation and change in ACQ scores. Of the 2442 patients who reported allergic rhinitis symptoms at baseline, 91% showed a global improvement of their asthma symptoms and 82% in their rhinitis symptoms after adding montelukast.. This open-label observational study showed an improvement, after 2 months of add-on therapy with montelukast, in both asthma and allergic rhinitis symptoms in patients not adequately controlled on a fixed association of ICS/LABA.

Topics: Acetates; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Belgium; Budesonide; Cyclopropanes; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Quinolines; Salmeterol Xinafoate; Sulfides; Surveys and Questionnaires

Conventional spacers help overcome problems with co-ordination and may improve lung deposition and decrease oropharyngeal impaction. Antistatic spacers eliminate electrostatic charge and may hence improve respirable dose delivery. The systemic bioavailability of inhaled fluticasone propionate is primarily dependent on delivery by the pulmonary route and hence the performance of antistatic spacers can be evaluated using adrenal suppression as a sensitive surrogate for relative bioavailability to the lung after an inhalation.. This study compares the relative bioavailability to the lung of inhaled fluticasone delivered via conventional pressurized metered dose inhalers (pMDI) and three antistatic spacers (plastic Zerostat-V, plastic Aerochamber Max, and metal Nebuchamber) in patients with asthma. All three antistatic spacers when compared with pMDI significantly increased the relative bioavailability to the lungs of inhaled fluticasone in terms of relative adrenal suppression, and there were no significant differences between the plastic and metal antistatic spacers.. The systemic bioavailability of inhaled fluticasone propionate (FP) depends primarily on lung absorption and can be quantified by measuring suppression of overnight and early morning urinary cortisol/creatinine (OUCC and EMUCC, respectively). The aim of the study was to determine the relative bioavailability of hydrofluoroalkane (HFA) FP to the lungs via anti-static plastic (Zerostat-V and Aerochamber Max), metal (Nebuchamber) anti-static spacers and metered dose inhaler [Flixotide Evohaler (EH) (pMDI)].. A randomized, double-blind, double-dummy, four-way crossover design was used. Eighteen mild to moderate asthmatics received single doses of placebo/HFA-FP 2 mg via the 280-ml Zerostat-V (ZS); 250-ml Nebuchamber (NC); 197-ml Aerochamber Max (AC); and pMDI (EH). Measurements of OUCC and EMUCC were made at baseline and 10 h after each dose.. Significant suppression of OUCC and EMUCC occurred from baseline with all three spacers, but not Evohaler (geometric mean fold suppression, 95% confidence interval): ZS, 2.74 (1.75, 4.30), P < 0.001; NC, 3.31 (1.81, 6.06), P < 0.001; AC, 4.98 (3.39, 7.31), P < 0.001; and for EH this was 1.42 (0.92, 2.21), P= 0.169 (equating to a 64, 70, 80 and 30% fall in OUCC via the ZS, NC, AC and EH devices, respectively). There were significant differences between all three spacers vs. EH. When compared with the Evohaler, the Zerostat V resulted in 48% greater suppression (P= 0.009); the Nebuchamber 57% greater suppression (P= 0.001); and the Aerochamber Max 71% greater suppression of OUCC (P < 0.001).. All three antistatic spacers significantly increased the relative systemic bioavailability of HFA-FP compared with the standard pMDI. --EudraCT Database trial registration number: 2005-005557-22.

Topics: Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Biological Availability; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Male; Metered Dose Inhalers; Middle Aged; Treatment Outcome; Young Adult

Regular use of inhaled beta(2)-agonists has been associated with a paradoxical loss of asthma control and a deterioration of airway hyper-responsiveness, but the underlying mechanism is unknown. The neurotrophin brain-derived neurotrophic factor (BDNF) has recently been identified as a mediator of airway hyper-responsiveness in asthma.. Eighteen patients with mild allergic asthma who did not use any regular antiasthmatic therapy inhaled the long-acting beta(2)-agonist salmeterol for 2 weeks followed by 2 weeks of combination therapy with salmeterol and the corticosteroid fluticasone. Airway responsiveness to histamine and BDNF concentrations in blood were assessed prior to entry, after 14 days of salmeterol therapy and after 14 days of combination therapy. In a separate experiment, salmeterol effects on BDNF release by human peripheral blood mononuclear cells were assessed.. Monotherapy with salmeterol significantly increased BDNF concentrations in serum and platelets. This increase was abolished by the addition of fluticasone to the treatment. The findings were confirmed in vitro: salmeterol increased the release of BDNF by mononuclear cells, and this was inhibited by co-incubation with fluticasone. Increased BDNF concentrations in serum and platelets correlated with the deterioration of airway hyper-responsiveness following salmeterol monotherapy. In contrast, there was no association between beta(2)-receptor polymorphisms and changes in airway responsiveness.. Increased BDNF concentrations may underly the adverse effects of salmeterol monotherapy on airway responsiveness in asthma.. NCT00736801.

Topics: Adolescent; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Brain-Derived Neurotrophic Factor; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Histamine; Humans; Leukocytes, Mononuclear; Male; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Salmeterol Xinafoate; Young Adult

There is a large body of data to support the use of an inhaled corticosteroid (ICS) plus a long-acting beta(2)-agonist vs. increasing the dose of ICS in adults, but less data in children. This double-blind, parallel group, non-inferiority study compared lung function and asthma control, based on Global Initiative for Asthma guidelines, in children receiving either salmeterol/fluticasone propionate (SFC) 50/100 microg bd (n = 160) or fluticasone propionate (FP) 200 microg bd (n = 161) for 12 wks. Change from baseline in mean morning peak expiratory flow increased following both treatments, but was significantly greater in the SFC group compared with FP [Adjusted mean change (s.e.) (l/min): SFC: 26.9 (2.13), FP: 19.3 (2.12); treatment difference: 7.6 (3.01); 95% CI: 1.7, 13.5; p = 0.012)]. Asthma control improved over time in both groups. Mean pre-bronchodilator maximal-expiratory flow at 50% vital capacity and percentage rescue-free days showed significantly greater improvements in the SFC group compared with FP. All other efficacy indices showed comparable improvements in each group. Treatment with SFC 50/100 microg bd compared with twice the steroid dose of FP (200 microg bd), was at least as effective in improving individual clinical outcomes and overall asthma control, in asthmatic children previously uncontrolled on low doses of ICS.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Europe; Female; Fluticasone; Humans; Lung; Male; Salmeterol Xinafoate; Treatment Outcome

Current asthma guidelines emphasize domains of impairment and risk for assessing severity and control, noting the need to consider separately the effects of asthma on asthma quality of life and functional capacity. Proper treatment to control asthma should result in improvements in patient well-being and functional status.. To assess asthma-related quality of life after treatment with combination fluticasone propionate and salmeterol delivered via hydrofluoroalkane 134a metered-dose inhaler compared with the individual components alone.. Asthma-related quality of life was assessed as part of two 12-week, randomized, double-blind, placebo-controlled clinical trials comparing the fluticasone propionate-salmeterol combination administered via a single metered-dose inhaler with salmeterol, fluticasone propionate, and placebo administered via traditional chlorofluorocarbon metered-dose inhaler. The Asthma Quality of Life Questionnaire was completed at baseline and end point. Score changes, overall and for the 4 separate domains, were compared within and among the treatment groups.. A total of 720 of 725 patients completed a baseline Asthma Quality of Life Questionnaire and were included in the analyses. In both studies, all mean scores improved significantly from baseline with the fluticasone propionate-salmeterol combination, with significantly greater improvement in the overall score compared with salmeterol alone, fluticasone propionate alone, and placebo groups. Improvements with the combination were also clinically meaningful compared with changes with salmeterol and placebo in both studies and with fluticasone propionate in study 1.. Treatment with combination fluticasone propionate and salmeterol delivered via hydrofluoroalkane metered-dose inhaler resulted in significantly greater improvements in asthma-related quality of life compared with individual components and placebo administered via traditional chlorofluorocarbon metered-dose inhaler.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Quality of Life; Salmeterol Xinafoate; Surveys and Questionnaires; Treatment Outcome; United States

The recently released handheld In-Check device can be used to measure the peak inspiratory flow rate (PIF) of patients and is reportedly useful in determining whether the PIF is sufficient for using inhaler devices. In this study, we evaluated the effects of instructions for the use of the device and of the device type based on measurements of the PIF in asthma.. One hundred and thirty-five asthmatic patients who used a fluticasone propionate Diskus (FP-DK) or a budesonide Turbuhaler (BUD-TH) were studied.. The PIF was measured by the In-Check device. For patients without a sufficient PIF of 50 l/min, instructions for the use of the device were given, and the device was changed to hydrofluoroalkan-beclomethasone dipropionate (HFA-BDP).. A significant correlation between the PIF and peak expiratory flow rate (p < 0.0001) was found. In 10 patients in whom the PIF did not increase to >50 l/min after instructions, the device was changed to HFA-BDP, which resulted in significant improvements in lung function in terms of the forced expiratory volume in 1 s (p = 0.018), peak expiratory flow (p = 0.038) and the maximum expiratory flow rates at 50% (p = 0.018) and 25% (p = 0.011).. Measurement of the PIF by the In-Check device is useful in the clinical management of asthma, to provide an appropriate device so as to improve lung function.

Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Androstadienes; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Female; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Inhalation; Male; Middle Aged; Respiratory Function Tests

Salmeterol and fluticasone propionate combination (SFC) provides better asthma control than fluticasone propionate (FP) alone, however, little is known on the effects of differential treatments on airway function and inflammation in patients with mild asthma.. We randomized 27 mild persistent asthma patients treated with the equivalent of 400 microg beclomethasone dipropionate to receive SFC (50/100 microg , 13 patients) or FP (100 microg , 14 patients) twice daily for 8 weeks. We compared the effects of SFC and FP on pulmonary function assessed by spirometry and impulse oscillometry (IOS), eosinophil percentage of induced sputum and serum, and with asthma symptoms and control after each treatment.. We observed that SFC significantly improved forced expiratory volume in one second (p < 0.05), IOS measurements of total resistance R5 (p < 0.01), central resistance R20 (p < 0.05), and distal reactance X5 (p < 0.01) compared with FP. The percentage of eosinophils in sputum, but not in serum, decreased significantly more in the SFC group than in the FP group (p < 0.05). There was also a significant improvement in symptom control in the SFC group (p < 0.05).. These findings suggest that SFC is more useful than FP in mild asthma cases. The clinical benefit of SFC provides evidence that IOS and induced sputum allows for the detection of changes in airway function and inflammation.

Topics: Adult; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Drug Combinations; Eosinophils; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Leukocyte Count; Male; Middle Aged; Oscillometry; Spirometry; Sputum; Treatment Outcome

Measuring non-invasive exhaled biomarkers of inflammation may be important in monitoring asthma therapy.. Evaluate exhaled nitric oxide with add-on leukotriene synthesis inhibitor in moderate-severe persistent asthmatics on combination controllers.. In a non-randomized, non-placebo, single-blind, fixed sequence, pilot study, we evaluated 22 non-smoking, stable, moderate-severe adult asthmatics on maintenance inhaled fluticasone 250 microg/salmeterol 50 microg (F/S) via MDI bid> or =1 yr, with add-on oral zileuton 600 mg qid. Exhaled fractional nitric oxide (FENO) gas exchange, large airway NO, small airway/alveolar NO concentration (CANO), Juniper score and lung function were measured. Asthmatics were studied at baseline only on F/S bid (visit 1), on F/S bid pre and 2 h post first dose zileuton 600 mg (visit 2), and post 4 weeks (visit 3) F/S bid plus zileuton 600 mg qid. Values were compared at each visit and to healthy non-smoking age matched healthy controls with normal lung function.. Three asthmatics stopped zileuton prematurely (headache and/or nausea) and 19 (12F) age 55+/-17 yr (mean+/-SD) completed the 4-week study. Baseline forced expiratory lung volume in 1 sec (FEV(1)) was 1.6+/-0.7L (53+/-19% pred) (mean+/-SD), FEV(1) over FVC ratio was 64+/-11% and post 180 microg albuterol FEV(1) was 1.8+/-0.7L (56+/-21% pred), and FEV(1) over FVC ratio was 67+/-12%. Baseline Juniper scores were mild (10+/-10) and similar (p=ns) at all visits. Baseline FENO@50 mL/s was 48+/-27 ppb (mean+/-SD), and FENO@100 mL/s was 29+/-16ppb, and were similar (p=ns) at all visits. Large airway NO flux was 2.0+/-1.3 nL/s (52% asthmatics abnormal) and small airway/alveolar NO was 8.0+/-4.0 ppb (79% asthmatics abnormal) and were similar (p=ns) at all visits. Compared to baseline, post 26+/-6 days Zileuton, mean FEV(1) (L)% predicted increased 3.3% predicted (p=0.03), and FEV(1) over FVC ratio increased 2.2% (p=0.03).. In stable, moderate-severe persistent adult asthmatics, large airway NO flux, small airway/alveolar CANO, and Juniper airway scores, were not significantly different on F/S bid vs F/S bid plus Zileuton for 4 weeks, despite significant small increase in FEV(1) over FVC ratio and FEV(1)% predicted.

Topics: Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Drug Therapy, Combination; Eosinophils; Female; Fluticasone; Humans; Hydroxyurea; Juniperus; Leukocyte Count; Male; Middle Aged; Nitric Oxide; Prospective Studies; Pulmonary Alveoli; Respiratory Function Tests; Respiratory System; Salmeterol Xinafoate; Spirometry

T-helper type 2 (Th2) inflammation, mediated by IL-4, IL-5, and IL-13, is considered the central molecular mechanism underlying asthma, and Th2 cytokines are emerging therapeutic targets. However, clinical studies increasingly suggest that asthma is heterogeneous.. To determine whether this clinical heterogeneity reflects heterogeneity in underlying molecular mechanisms related to Th2 inflammation.. Using microarray and polymerase chain reaction analyses of airway epithelial brushings from 42 patients with mild-to-moderate asthma and 28 healthy control subjects, we classified subjects with asthma based on high or low expression of IL-13-inducible genes. We then validated this classification and investigated its clinical implications through analyses of cytokine expression in bronchial biopsies, markers of inflammation and remodeling, responsiveness to inhaled corticosteroids, and reproducibility on repeat examination.. Gene expression analyses identified two evenly sized and distinct subgroups, "Th2-high" and "Th2-low" asthma (the latter indistinguishable from control subjects). These subgroups differed significantly in expression of IL-5 and IL-13 in bronchial biopsies and in airway hyperresponsiveness, serum IgE, blood and airway eosinophilia, subepithelial fibrosis, and airway mucin gene expression (all P < 0.03). The lung function improvements expected with inhaled corticosteroids were restricted to Th2-high asthma, and Th2 markers were reproducible on repeat evaluation.. Asthma can be divided into at least two distinct molecular phenotypes defined by degree of Th2 inflammation. Th2 cytokines are likely to be a relevant therapeutic target in only a subset of patients with asthma. Furthermore, current models do not adequately explain non-Th2-driven asthma, which represents a significant proportion of patients and responds poorly to current therapies.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Biomarkers; Bronchi; Bronchodilator Agents; Female; Fluticasone; Genetic Heterogeneity; Humans; Inflammation; Macrophages, Alveolar; Male; Mucins; Phenotype; Pulmonary Fibrosis; Respiratory Mucosa; Th2 Cells; Treatment Outcome

With the expanding effort to provide guidelines-based therapy to adolescents with asthma, attention must be directed to evaluating which factors predict future asthma control when guidelines-based management is applied.. We evaluated the role of fraction of exhaled nitric oxide in parts per billion, markers of allergic sensitization, airway inflammation, and measures of asthma severity in determining future risk of asthma symptoms and exacerbations in adolescents and young adults participating in the Asthma Control Evaluation study.. Five hundred forty-six inner-city residents, ages 12 through 20 years, with persistent asthma were extensively evaluated at study entry for predictors of future symptoms and exacerbations over the subsequent 46 weeks, during which guidelines-based, optimal asthma management was offered. Baseline measurements included fraction of exhaled nitric oxide in parts per billion, total IgE, allergen-specific IgE, allergen skin test reactivity, asthma symptoms, lung function, peripheral blood eosinophils, and, for a subset, airway hyperresponsiveness and sputum eosinophils.. The baseline characteristics we examined accounted for only a small portion of the variance for future maximum symptom days and exacerbations--11.4% and 12.6%, respectively. Future exacerbations were somewhat predicted by asthma symptoms, albuterol use, previous exacerbations, and lung function, whereas maximum symptom days were predicted, also to a modest extent, by symptoms, albuterol use, and previous exacerbations, but not lung function.. Our findings demonstrate that the usual predictors of future disease activity have little predictive power when applied to a highly adherent population with persistent asthma that is receiving guidelines-based care. Thus, new predictors need to be identified that will be able to measure the continued fluctuation of disease that persists in highly adherent, well-treated populations such as the one studied.

Topics: Acetates; Adolescent; Adrenergic beta-Agonists; Albuterol; Allergens; Androstadienes; Anti-Asthmatic Agents; Asthma; Biomarkers; Child; Cyclopropanes; Double-Blind Method; Exhalation; Female; Fluticasone; Follow-Up Studies; Humans; Immunoglobulin E; Male; Nitric Oxide; Patient Compliance; Practice Guidelines as Topic; Quinolines; Salmeterol Xinafoate; Skin Tests; Sulfides; Urban Population; Young Adult

Current guidelines suggest that asthma should be controlled with the lowest dose of maintenance medication required.. To evaluate the effects of a low dose of inhaled corticosteroid compared to a placebo, on airway inflammation and responsiveness in patients with mild symptomatic asthma.. In this randomized double-blind, placebo-controlled, parallel group study, we looked at the influence of inhaled fluticasone propionate 250 microg/day for 3 months followed by 100 microg/day for 9 months on airway inflammation and methacholine responsiveness in non-smoking subjects with mild allergic asthma. Subjects were evaluated at baseline and 3, 6, 9 and 12 months after treatments; a 2-week evaluation of respiratory symptoms and peak expiratory flow measurements was done before each visit.. Fifty-seven subjects completed the 3-month study period. Airway responsiveness, expressed as the PC20 methacholine, increased by 0.27 and 1.14 doubling concentrations, respectively, in placebo-treated (n=33) and in fluticasone-treated (n=24) asthmatic subjects (p=0.03). An additional improvement in PC20 up to 2.16 doubling concentrations was observed in the fluticasone-treated group during the 9-month lower-dose treatment (p=0.0004, end of low-dose period compared with placebo). Sputum eosinophil counts decreased after 3 months of fluticasone 250 microg/day compared with placebo (p<0.0001) and remained in the normal range during the 9-month lower-dose treatment. Respiratory symptoms and peak expiratory flows did not change significantly throughout the study in both groups.. In mild asthma, keeping a regular minimal dose of ICS after asthma control has been achieved, may lead to a further reduction in airway responsiveness and keep sputum eosinophil count within the normal range.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Practice Guidelines as Topic; Young Adult

Factors affecting the fraction of nitric oxide in exhaled air (FE(NO)) are multiple. Interpreting values when assessing airways disease may be problematic. Clinically optimum levels have not been defined.. We aimed to establish the relationship between predicted values for FE(NO) obtained from equations by Olin et al, Travers et al, and Dressel et al, and normalized levels after oral prednisone. We also compared postprednisone FE(NO) levels with those obtained during optimized treatment with inhaled fluticasone.. Data were obtained before and after a trial of oral prednisone (30mg/d for 14 days), and also from a previously published study in which patients had their dose of inhaled corticosteroid adjusted using either FE(NO) or symptoms/lung function to optimize treatment.. Seventy-three patients completed the study. The geometric mean FE(NO) after prednisone (17.7 parts per billion [ppb]; 95% CI, 15.5-20.2) was significantly lower than mean FE(NO) at the optimized fluticasone dose (20.2 ppb; 95% CI, 17.1-23.8; P=.04) and at loss of control (27.6 ppb; 95% CI, 22.8-33.4; P < .001). FE(NO) levels after prednisone did not differ significantly from the predicted values of Olin et al (16.8 ppb, 95% CI, 16.0-17.5; P=.44), but were significantly lower than values of Travers et al (predicted, 21.5 ppb; 95% CI, 20.9-22.2; P=.005) and Dressel et al (predicted, 27.8 ppb; 95% CI, 26.7-28.9; P < .001).. Optimum FE(NO) levels are best established by using oral rather than inhaled steroid treatment, and these approximate to predicted values from the reference equation by Olin et al. However, at optimized doses of inhaled corticosteroid, although FE(NO) levels were higher than predicted, asthma was well controlled. Targeting FE(NO) on reference values is not justified.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Androstadienes; Asthma; Breath Tests; Exhalation; Female; Fluticasone; Humans; Male; Middle Aged; Nitric Oxide; Prednisone; Reference Values; Young Adult

Exhaled breath condensate (EBC) measurements have recently been reported to be useful for the detection of inflammatory molecules in the airways. However, the clinical relevance of EBC analysis in asthma therapy has not been determined yet.. To investigate whether EBC analysis has any potential for predicting the steroid response in asthmatics.. Eighteen steroid-naive asthmatics were enrolled. EBC collection, spirometry and a methacholine challenge test were performed before and 12 weeks after inhaled steroid therapy. Exhaled IL-4, IL-17, RANTES, macrophage inflammatory protein (MIP)-1α, MIP-1β, IL-8, IFN-γ-inducible protein (IP)-10, TNF-α and TGF-β were simultaneously analyzed by a protein array, and the relationship between baseline molecule expression and steroid-mediated changes in forced expiratory volume in 1 s (FEV1) and airway responsiveness was investigated.. Steroid therapy improved FEV1 values and the methacholine threshold. Among the molecules examined, increased IL-4 and RANTES levels as well as decreased IP-10 levels at baseline were significantly correlated with an improvement in FEV1. By contrast, molecule levels were not related to changes in the responsiveness to methacholine. In addition, changes in FEV1 values were significantly associated with reductions in IL-4 and RANTES levels.. EBC measurements of IL-4, RANTES and IP-10 might be useful for predicting the steroid-mediated FEV1 improvement in asthma.

Topics: Adrenergic beta-2 Receptor Agonists; Adult; Androstadienes; Asthma; Breath Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Cytokines; Fluticasone; Forced Expiratory Volume; Humans; Methacholine Chloride; Predictive Value of Tests

In asthmatic children whose symptoms are uncontrolled on standard doses of inhaled corticosteroids (ICS), guidelines recommend to either increase the ICS dose or to add further controller medication, e.g. a long acting ss2-agonist (LABA). The aim of this study was to compare the efficacy and safety of doubling the dose of ICS (fluticasone proprionate FP 200 microg twice daily) with adding a long-acting beta-2 agonist to the ICS (SFC, salmeterol 50 microg/ FP 100 microg twice daily) in children with uncontrolled asthma.. Children between 4 and 16 years of age were eligible for this multicenter, randomized, double blind, double dummy, parallel-group study. During a 14-day run-in phase, all children inhaled FP 100 microg b.i.d. Patients with persistent symptoms on > or =7 of 14 days were randomized to 8 weeks treatment with a Diskus(R) containing either SFC 50 microg/100 microg b.i.d. or FP 200 microg b.i.d.. The primary endpoint was the mean change in morning (a.m.) PEF from baseline. The initial statistical hypothesis of non-inferiority of SFC vs. FP was confirmed in an adaptive interim analysis, so that the study was terminated prematurely.. 441 patients from 39 centers entered the run-in phase, and 64% of these were randomized to treatment (N = 138 to SFC and N = 145 to FP). After 8 weeks, patients on SFC had significantly better results for primary and secondary endpoints: The mean increase in morning PEF was 30.4 +/- 34.1 L/min in the SFC group and 16.7 +/- 35.8 L/min in the fluticasone group, and the mean (95% CI) improvement from baseline a.m. PEF in the ITT group was significantly larger after SFC (+8.6 L/min, CI: [1.3; infinity]). Patients in the SFC group experienced 8.7% (CI: [1.2;16.3]) more days without asthma symptoms and 8.0% (CI: [0.6;15.3]) more days without salbutamol than patients receiving FP. Good asthma control was achieved for a longer period in the SFC (3.4 +/- 2.7 weeks) group than in the FP group (2.7 +/- 2.7, P = 0.02). Both treatments were generally well tolerated. Asthma exacerbations were recorded in 3 and 6 and SAEs in 2 and 1 patients from the SFC and FP groups, respectively.. In children with persistent asthma inadequately controlled on low dose ICS alone, adding a long acting beta-2-agonist to ICS in a single inhaler was more effective than doubling the ICS dose. These results support recommendations of adding LABA to low-dose ICS as the preferred controller option for children older than 4 years with symptomatic asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Peak Expiratory Flow Rate; Salmeterol Xinafoate

We investigated if a higher proportion of adults with previously uncontrolled asthma can achieve total control when given salmeterol/fluticasone propionate (50/250 microg) bid and compliance enhancement training (CET) compared to those given medication alone.. Open comparison of stable, but uncontrolled, adult asthmatics. After a 12-week treatment period on salmeterol/fluticasone propionate (period 1), patients who failed to achieve control were randomised to continuing treatment with or without CET for 12 weeks (period 2). The primary end point was the proportion achieving total control of their asthma in 7 of the last 8 consecutive weeks of period 2.. A total of 361 subjects (50.4% males, mean age 40.0 +/- 14.4 years) in 29 centres were included, of whom 75.9% were randomised into treatment period 2 (n = 140 in the intervention group). The proportion of subjects achieving total asthma control was 8.8% and 7.6%, respectively, in the intervention and control group [not significant (NS)]. Mean morning peak flow, forced expiratory volume in one second (FEV(1)), asthma symptom score and quality of life improved significantly over the study period in both treatment groups. Furthermore, proportion of days with use of rescue medication declined from 59.7% +/- 34.6% (55.7% +/- 35.3%) during screening to 20.3% +/- 29.2% (19.4% +/- 30.9%) during treatment period 2 (NS).. CET failed to increase the likelihood of achieving total control in asthmatics on salmeterol/fluticasone propionate compared to subjects receiving medication only. However, both groups had a significant improvement in asthma control. (Clinical Trials.gov number, NCT00351143)

Topics: Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Denmark; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Patient Compliance; Salmeterol Xinafoate; Switzerland; Treatment Outcome

To compare the cost-effectiveness of budesonide/formoterol in a single inhaler used as Maintenance and Reliever Therapy (SMART) versus fixed higher-dose budesonide/formoterol plus as-needed terbutaline reliever (FHDBF) or fixed dose fluticasone/salmeterol plus as-needed terbutaline reliever (FDFS) in controlling asthma in adults and adolescents.. An economic evaluation was conducted by applying Canadian costs to the results of a large (N=3,335) international randomized, double-blind, controlled trial in which health resource utilization was prospectively collected. Although no Canadian subjects were enrolled in this clinical trial, it was assumed that the results would apply to Canadian patients. Primary outcome measurements included time to first exacerbation and the number of severe exacerbations. Costs included direct medical costs (physician/emergency room visits, hospitalizations, asthma drug costs) and productivity (absenteeism). The time horizon was six months, which corresponded to the duration of the trial. Prices were obtained from 2006 Canadian sources. Both healthcare and societal perspectives were considered. Deterministic univariate sensitivity analyses were conducted.. In the clinical trial, SMART was superior to FHDBF and FDFS with respect to total number of severe exacerbations (RR 0.72; 95% CI 0.57, 0.90; p=0.0048; RR 0.61; 95% CI 0.49, 0.76; p<0.001, respectively). Exacerbation rates (reported as events per patient per 6 months) were 0.12 for SMART, 0.16 for FHDBF, and 0.19 for FDFS. All treatments provided similar improvements in lung function, asthma control days and asthma-related quality of life. The mean cost per patient per 6 months was $545 in the SMART arm versus $690 in the FHDBF arm and $842 in the FDFS arm from the healthcare perspective; and $676 for SMART, $838 for FHDBF, and $954 for FDFS from the societal perspective. SMART was dominant (more effective, less expensive) in the base case analysis from both the healthcare and societal perspectives. The results were robust under sensitivity testing.. The SMART strategy, which allows budesonide/formoterol to be used as both maintenance and reliever medication, is dominant over the alternate strategies of fixed higher dose budesonide and formoterol plus as-needed terbutaline or fixed dose salmeterol and fluticasone plus as-needed terbutaline.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Canada; Child; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Prospective Studies; Quality of Life; Salmeterol Xinafoate; Severity of Illness Index; Terbutaline

Uncontrolled asthma is characterized by variability. Current asthma guidelines recommend focussing on the achievement and maintenance of control but few studies have examined in detail, using composite measures of control, the stability and potential duration of control once achieved. In this post-hoc analysis of the results of the Gaining Optimal Asthma controL (GOAL) study, we examine the association between the level of asthma control achieved during the step-up phase of the study and the stability of control experienced during the maintenance phase.. GOAL was a 1-year, randomized, stratified, double-blind study of 3421 patients with uncontrolled asthma, which compared salmeterol/fluticasone propionate combination with fluticasone propionate in achieving two composite, guideline-based measures of control: totally controlled and well-controlled asthma. We analysed the proportion and duration of time spent in control, the effect of treatment on asthma stability, and the impact of asthma control stability on unscheduled use of healthcare resources.. In patients achieving well-controlled or totally controlled asthma, at least well-controlled asthma was maintained for a median of almost 3 and 6 months, and for more than 85% and 95% of weeks of follow-up, respectively. A high level of stability was confirmed in a Markov analysis investigating transitional probability of change in control status. Variability in control was associated with increased probability of an unscheduled healthcare resource use (odds ratio: 1.06, P < 0.001).. Most patients achieving guideline-defined control can maintain at least a similar level of control with regular, stable dosing, with little likelihood of losing control.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Logistic Models; Markov Chains; Middle Aged; Odds Ratio; Time Factors

Extra-fine hydrofluoroalkane-beclomethasone differs from other inhaled corticosteroids by its fine aerosol characteristics. Therefore, extra-fine hydrofluoroalkane-beclomethasone may be particularly useful for treating peripheral airway inflammation in asthma.. To analyze the anti-inflammatory effects of extra-fine hydrofluoroalkane-beclomethasone vs fluticasone dry powder inhaler (DPI) in asthmatic children by measuring bronchial and alveolar nitric oxide (NO) and inflammatory markers in exhaled breath condensate (EBC).. In a 6-month crossover study, 33 children aged 6 to 12 years with moderate persistent asthma were randomly treated with extra-fine hydrofluoroalkane-beclomethasone (200 microg daily via an Autohaler) and fluticasone DPI (200 microg daily via a Diskus). The primary outcome variables were alveolar NO concentration and bronchial NO flux. The secondary outcome variables were levels of inflammatory markers in EBC, lung function indices, symptoms, exacerbations, and adverse effects. All the variables were recorded at baseline and after each treatment period.. Mean +/- SE alveolar NO concentration and bronchial NO flux were comparable after treatment with hydrofluoroalkane-beclomethasone vs fluticasone DPI (4.7 +/- 0.5 vs 4.3 +/- 0.5 ppb, P = .55, and 1,124.3 +/- 253.6 vs 1,029.1 +/- 195.5 pL/s, P = .70, respectively). In addition, levels of inflammatory markers in EBC, lung function indices, and symptoms did not differ between treatments. Patients used fewer beta2-agonists during the last 2 weeks of hydrofluoroalkane-beclomethasone treatment.. The anti-inflammatory effects of hydrofluoroalkane-beclomethasone are similar to those of fluticasone DPI in children with moderate persistent asthma.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biomarkers; Breath Tests; Child; Cross-Over Studies; Dinoprost; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrogen Peroxide; Inflammation; Interleukins; Male; Nitrates; Nitric Oxide; Nitrites; Prospective Studies; Treatment Outcome; Vital Capacity

In patients controlled with SFC250 Diskus bd, this double-blind, randomised 6-month study compared continuing SFC250 to stepping down to either SFC100 bd or FP250 bd. Six hundred and three patients previously using 1,000 microg BDP (or equivalent) daily +LABA and controlled according to investigator's judgement were recruited. Patients received SFC250 bd during an 8-week open run-in period. Four hundred and seventy six patients (mean age=43 years, mean FEV(1)=2.9+/-1.0) who fulfilled the randomisation criterion ('Well-controlled' asthma according to the GOAL weekly definition for the last 2 weeks of the run-in period) entered a 24-week treatment period. The statistical hypothesis was based on a non-inferiority of SFC100 or FP250 compared to SFC250. The main criterion was the change from baseline in morning PEF over weeks 1-12 in the per-protocol population. The non-inferiority limit was -15 L/min. At inclusion, the three treatment groups were well balanced. Mean morning PEF was 476, 470 and 465 L/min in the SFC250, SFC100 and FP250 groups, respectively. The adjusted mean change in morning PEF over weeks 1-12 was +1.76+/-2.43 L/min for SFC250, -3.07+/-2.32 L/min for SFC100 and -16.51+/-2.46 L/min for FP250. SFC100 was at least as effective as SFC250 (treatment difference -4.83 [-12.39; 2.72], p=0.151) whereas FP250 was not (treatment difference -18.27 [-26.05; -10.49], p<0.001). Similar results were observed over weeks 13-24 in morning PEF (SFC100-SFC250=-4.54+/-3.84, p=0.238; FP250-SFC250=-20.11+/-3.92, p<0.0001). Secondary endpoints showed a similar pattern. Over weeks 1-12, SFC250 was significantly more effective than FP250 on evening PEF, daily symptoms and bronchodilator use. There was no difference between SFC100 and SFC250. The mean annual rate of moderate exacerbations was 0.16 in both SFC 250 and SFC 100 groups, and 0.21 in FP 250 group (ns, Poisson analysis). All treatments were well tolerated.. In patients achieving asthma control with SFC250, stepping treatment down with SFC100 was at least as effective on lung function and symptoms as continuing SFC250, whereas FP250 was not.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Prospective Studies; Treatment Outcome; Young Adult

Beneficial effects of anti-inflammatory therapy such as fluticasone propionate (FP) and montelukast (Mk) have been demonstrated in preschool children with asthma. However, comparative studies are lacking in this age group. Therefore, we conducted a study to evaluate and compare the effect of FP and Mk in preschool children with asthma-like symptoms.. In this multicenter, randomized, placebo-controlled, double-blind, double-dummy trial, children aged 2-6 years with asthma-like symptoms were included. In total, 63 children were randomly allocated to receive FP (25), Mk (18) or placebo (20) for 3 months. The primary outcome was the daily symptom score (wheeze, cough, shortness of breath) as recorded by caregivers in a symptom diary card. Secondary endpoints were rescue medication free days, blood eosinophils and lung function (interrupter technique and forced oscillation technique (FOT)).. During the 3 months study period, symptoms improved in all 3 groups, with a statistically significant difference between FP and placebo in favor of the FP group (p=0.021). A significant reduction in circulating eosinophils after 3 months of treatment was found in the Mk group only (p=0.008), which was significantly different from the change found in the placebo group (p=0.045). With the exception of frequency dependence (measured by FOT), which showed a difference between FP and Mk after 3 months of treatment in favor of the FP group (p=0.048), no differences in lung function within or between groups were found.. In spite of a lack of power, our results suggest that FP has a beneficial effect on symptoms and Mk on blood eosinophil level as compared to placebo. Except for a difference in one lung function parameter after 3 months between FP and Mk in favor of the FP group, this study revealed no differences between FP and Mk.

Topics: Acetates; Administration, Oral; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child, Preschool; Cyclopropanes; Double-Blind Method; Female; Fluticasone; Humans; Male; Metered Dose Inhalers; Netherlands; Outpatient Clinics, Hospital; Quinolines; Respiratory Function Tests; Sulfides; Tablets; Time Factors; Treatment Outcome

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) signalling of regulatory T cells regulates mucosal lymphocyte tolerance and differentiation, and may therefore have a beneficial effect in allergic diseases such as asthma. The aim of this study was to evaluate the effects of fluticasone propionate (FP) on CD4+CD25+ T cell co-expression of CTLA-4 in the sputum of mild asthmatic subjects.. Eleven mild, stable asthmatic subjects completed a double-blind, randomized, crossover, placebo-controlled study to compare the effects of 14 days 200 microg twice daily FP and placebo. Before and after treatment, airway hyperresponsiveness was measured, and sputum was induced for measurements of CTLA-4+CD4+CD25+ cells, eosinophils and levels of IL-10, IL-13 and transforming growth factor (TGF)-beta.. FP treatment increased co-expression of CTLA-4 on sputum CD4+CD25+ cells from a mean (SEM) of 7.9% (1.8) to 12.7% (3.3) after 14 days treatment (P < 0.05) compared with placebo. FP treatment also significantly increased IL-10 levels, reduced per cent sputum eosinophils, and reduced airway hyperresponsiveness (P < 0.05). There was a significant negative correlation between the change in airway hyperresponsiveness and per cent sputum eosinophils (P < 0.01), but no correlation with changes in CTLA-4+CD4+CD25+ cells (P > 0.05). There was no change in the levels of sputum IL-13 or TGF-beta.. The percentage of airway CTLA-4+CD4+CD25+ cells increased after FP treatment, coincident with improvements in airway inflammation and hyperresponsiveness.Whether improved asthma assessments are related to the increase in CTLA-4+CD4+CD25+ cells and thus improved regulation of T-cell tolerance and differentiation will require a larger sample size to determine. The normalization of CTLA-4+CD4+CD25+ cells in asthma may contribute to the management of this disease.

Topics: Administration, Inhalation; Adult; Androstadienes; Antigens, CD; Asthma; Bronchodilator Agents; CD4-Positive T-Lymphocytes; Cross-Over Studies; CTLA-4 Antigen; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Fluticasone; Follow-Up Studies; Humans; Interleukin-2 Receptor alpha Subunit; Lymphocyte Count; Male; Severity of Illness Index; Sputum; Young Adult

The role of inhaled corticosteroids in the treatment of acute asthma exacerbations in children is controversial. This study compared the effect of inhaled budesonide and inhaled fluticasone in controlling acute asthma exacerbations in young children at home.. In a quasi-randomized crossover design, children aged 5 months to 5 years with severe recurrent asthma episodes were treated either with inhaled budesonide 200 mcg or inhaled fluticasone 125 mcg delivered with a similar spacer. At the onset of asthma exacerbations, 2 puffs of inhaled terbutaline followed by inhaled budesonide or fluticasone was administered using one of the following treatment protocols: 1 4-day protocol for a relatively mild exacerbation; 2 8-day protocol for exacerbations that were more severe or uncontrolled by the 4-day protocol; and 3 8-day protocol + azithromycin for exacerbations uncontrolled by the 8-day protocol or possibly associated with infection with atypical agents. Children were followed for 2 months after each exacerbation. Good response was defined as the absence of asthma symptoms for at least 2 weeks from completion of treatment.. One hundred children were recruited: 36 were treated with budesonide, 21 with fluticasone, and 44 with both on different occasions. The groups were similar for preliminary data. Good response was noted in 87% of the budesonide group, 85% of the fluticasone group, and 86% of the budesonide/fluticasone group. By protocol, rates of good response were 84%, 83%, and 94% for the 4-day, 8-day, and 8-day+azithromycin treatment protocols, respectively; corresponding symptom-free periods after treatment were 4.0, 4.9, and 4.3 weeks. None of the children received oral corticosteroids.. Acute asthma exacerbations in young children can be effectively controlled at home with the use of high repetitive doses of inhaled budesonide or inhaled fluticasone, initially together with beta(2)-agonists, given at the beginning of the attack, for a period of 4-8 days.

Topics: Acute Disease; Administration, Inhalation; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Drug Therapy, Combination; Female; Fluticasone; Humans; Infant; Inhalation Spacers; Male; Severity of Illness Index; Terbutaline; Treatment Outcome

Asthma control remains suboptimal in adults and children worldwide. Inhaled salmeterol/fluticasone propionate combination (SFC) and oral montelukast (MON) are 2 treatments available for childhood asthma.. This study, the PEdiatric Asthma Control Evaluation (PEACE), investigated the efficacy and tolerability of SFC compared with MON for the control of persistent asthma in children.. Children with asthma (forced expiratory volume in 1 second [FEV(1)] 55%-80% predicted; reversibility >or=12%) aged 6 to 14 years who were receiving only short-acting beta(2)-agonists entered a 2-week run-in period. Symptomatic patients (rescue use or symptoms during 4 of the last 7 days) were randomized to double-blind, double-dummy treatment with SFC 50/100 microg BID via multidose dry powder inhaler or MON 5-mg tablet QD for 12 weeks. The primary end point was change from baseline in morning peak expiratory flow (PEF). Efficacy assessments included lung function, asthma symptoms, rescue medication use, and asthma control. Tolerability was assessed by recording the number and type of adverse events (AEs) and the number of asthma exacerbations.. Of 607 patients screened, 548 were randomized to treatment. The SFC group contained 281 patients and the MON group included 267. Demographic characteristics and baseline data were similar for both groups (mean age, 9.3 years for both groups; mean [SD] FEV(1), 1.49 [0.43] L in the SFC group and 1.48 [0.43] L in the MON group). There were more males in the MON group (179 [67%]) than in the SFC group (156 [56%]). The adjusted mean (SE) changes from baseline in morning PEF were 45.88 (2.82) L/min with SFC and 28.7 (2.86) L/min with MON (treatment difference, 17.16 L/min; 95% CI, 9.23-25.08; P < 0.001). Compared with MON, the SFC group had significantly more asthma symptom-free days (odds ratio [OR], 1.74; 95% CI, 1.07-2.82; P = 0.025), more rescue-free days (OR, 3.24; 95% CI, 2.09-5.02; P < 0.001), and more asthma-controlled weeks (difference in treatment medians over weeks 1-12, 16.77%; 95% CI, 8.3-16.77; P < 0.001). Both treatments were well tolerated, with a similar number of patients reporting AEs (SFC group, 155/281 [55%]; MON group, 153/267 [57%]); the most common AE in both groups was headache (SFC group, 66 [23%]; MON group, 72 [27%]). The mean exacerbation rates over 12 weeks (post hoc analysis) were 0.12 in the SFC group and 0.30 in the MON group (SFC/MON ratio, 0.40; 95% CI, 0.29-0.57; P < 0.001).. In these children with uncontrolled asthma previously on short-acting beta(2)-agonist monotherapy (% predicted FEV(1) <80%, frequent asthma symptoms and rescue medication use), treatment with SFC was significantly more effective in improving morning PEF and other measures of asthma control and in decreasing exacerbation rates (in a post hoc analysis) than treatment with MON. The 2 drugs were both well tolerated, with similar numbers and types of AEs reported.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Cyclopropanes; Double-Blind Method; Drug Combinations; Female; Fluticasone; Humans; Male; Peak Expiratory Flow Rate; Prospective Studies; Quality of Life; Quinolines; Sulfides

Preliminary evidence is equivocal about the role of exhaled nitric oxide (NO) in clinical asthma management. We aimed to assess whether measurement of exhaled NO, as a biomarker of airway inflammation, could increase the effectiveness of asthma treatment, when used as an adjunct to clinical care based on asthma guidelines for inner-city adolescents and young adults.. We did a randomised, double-blind, parallel-group trial at ten centres in the USA. We screened 780 inner-city patients, aged 12-20 years, who had persistent asthma. All patients completed a run-in period of 3 weeks on a regimen based on standard treatment. 546 eligible participants who adhered to treatment during this run-in period were then randomly assigned to 46 weeks of either standard treatment, based on the guidelines of the National Asthma Education and Prevention Program (NAEPP), or standard treatment modified on the basis of measurements of fraction of exhaled NO. The primary outcome was the number of days with asthma symptoms. We analysed patients on an intention-to-treat basis. This trial is registered with clinicaltrials.gov, number NCT00114413.. During the 46-week treatment period, the mean number of days with asthma symptoms did not differ between the treatment groups (1.93 [95% CI 1.74 to 2.11] in the NO monitoring group vs 1.89 [1.71 to 2.07] in the control group; difference 0.04 [-0.22 to 0.29], p=0.780). Other symptoms, pulmonary function, and asthma exacerbations did not differ between groups. Patients in the NO monitoring group received higher doses of inhaled corticosteroids (difference 119 mug per day, 95% CI 49 to 189, p=0.001) than controls. Adverse events did not differ between treatment groups (p>0.1 for all adverse events).. Conventional asthma management resulted in good control of symptoms in most participants. The addition of fraction of exhaled NO as an indicator of control of asthma resulted in higher doses of inhaled corticosteroids, without clinically important improvements in symptomatic asthma control.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Androstadienes; Asthma; Breath Tests; Bronchodilator Agents; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Nitric Oxide; Treatment Outcome; Urban Population

In this study, 647 subjects stable on fluticasone propionate/salmeterol Diskus 100/50 mcg BID (FSC) were randomized to continue FSC 100/50 mcg BID or "step down" to either fluticasone propionate (FP) 100 mcg BID, salmeterol (SAL) 50 mcg BID, or montelukast (MON) 10 mg once daily for 16 weeks. Overall asthma control significantly improved in the FSC group; whereas, "stepping down" to FP, SAL, or MON resulted in deterioration in asthma control, as determined by decreased measures of lung function and clinical features. This study provides support that treatment of both inflammation and smooth muscle dysfunction may be necessary to achieve and maintain asthma control in patients uncontrolled on ICS.

Topics: Acetates; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Flow Rates; Humans; Kaplan-Meier Estimate; Male; Patient Satisfaction; Peak Expiratory Flow Rate; Quinolines; Salmeterol Xinafoate; Sulfides; Surveys and Questionnaires

Asthma exacerbations are a common cause of critical illness in children.. To determine factors associated with exacerbations in children with persistent asthma.. Regression modeling was used to identify historical, phenotypic, treatment, and time-dependent factors associated with the occurrence of exacerbations, defined by need for oral corticosteroids or emergency or hospital care in the 48-week Pediatric Asthma Controller Trial study. Children age 6 to 14 years with mild-to-moderate persistent asthma were randomized to receive either fluticasone propionate 100 microg twice daily (FP monotherapy), combination fluticasone 100 microg AM and salmeterol twice daily, or montelukast 5 mg once daily.. Of the 285 participants randomized, 48% had 231 exacerbations. Using a multivariate analysis, which included numerous demographic, pulmonary, and inflammatory parameters, only a history of an asthma exacerbation requiring a systemic corticosteroid in the past year (odds ratio [OR], 2.10; P < .001) was associated with a subsequent exacerbation during the trial. During the trial, treatment with montelukast versus FP monotherapy (OR, 2.00; P = .005), season (spring, fall, or winter vs summer; P < or = .001), and average seasonal 5% reduction in AM peak expiratory flow (OR, 1.21; P = .01) were each associated with exacerbations. Changes in worsening of symptoms, beta-agonist use, and low peak expiratory flow track together before an exacerbation, but have poor positive predictive value of exacerbation.. Children with mild-to-moderate persistent asthma with previous exacerbations are more likely to have a repeat exacerbation despite controller treatment. Inhaled corticosteroids are superior to montelukast at modifying the exacerbation risk. Available physiologic measures and biomarkers and diary card tracking are not reliable predictors of asthma exacerbations.

Topics: Adolescent; Adrenal Cortex Hormones; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Longitudinal Studies; Male; Models, Biological; Multivariate Analysis; Regression Analysis; Salmeterol Xinafoate; Time Factors

In the Asia-Pacific region there is a general preference for prescribing oral over inhaled medications for the treatment of asthma. This study compared inhaled salmeterol/fluticasone propionate therapy (SFC) with physician-determined current care (CC) in the management of persistent asthma in Korea.. Adult patients with a documented history of reversibility in FEV(1) (>or= 12%) or PEF (>or= 15%), were randomised in a 2:1 ratio to unblinded treatment with SFC (50/250 microg bd or 50/500 microg bd) via Diskus (N = 284) or CC (N = 140) for 52 weeks. Morning peak expiratory flow (PEF) (primary endpoint), exacerbations, asthma symptoms and patient-reported outcome measures were recorded.. GSK study number:100614.. At baseline, mean morning PEF in the SFC and CC group was 374 and 401 L/min respectively. The adjusted mean morning PEF at 52 weeks was 423 +/- 3 and 396 +/- 4 L/min for SFC and CC respectively (treatment difference of 27 +/- 5 in favour of SFC; 95% CI 17, 37; p < 0.0001). The mean rate of exacerbations over 52 weeks was significantly lower in the SFC group (SFC/CC odds ratio 0.57; 95% CI 0.44, 0.74; p < 0.0001). Treatment with SFC also resulted in a significantly greater improvement in asthma symptoms, in the number of patients assessed to have well controlled asthma (Asthma Control Test score >or= 20), and in a clinically significant improvement in overall Quality of Life. The incidence of adverse events was low and similar between the two groups and events were of the type expected in this population.. The results of this open-label, randomised study showed that SFC provided greater asthma control than CC in the management of persistent asthma.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asian People; Asthma; Bronchodilator Agents; Female; Fluticasone; Humans; Korea; Male; Middle Aged; Salmeterol Xinafoate

The addition of a long-acting beta2 agonist (LABA) to inhaled corticosteroid (ICS) may control asthma better than ICS alone. Eosinophil markers may predict symptom severity in asthma.. The effect of combination treatment on moderate to severe asthmatics not selected to respond rapidly to steroid deprivation was compared with monotherapy. The ability of serum markers to predict symptom severity was assessed.. Asthmatics treated adequately with ICS (750-1000 mcg ICS daily) were randomised to receive ICS (fluticasone propionate) + LABA (salmeterol) (500 mcg/50 mcg bd) or ICS alone (500 mcg bd). If asthma was controlled at clinic visits every 6 weeks, ICS dose was tapered until asthma exacerbated (hospitalisation, ICS above study medication, peak flow variation, decline in forced expiratory volume in 1 s and/or use of rescue medication), or placebo was maintained for 6 weeks. Efficacy of the treatments was compared. Serum cytokines and chemokines were compared among the groups reporting severe, mild or no symptoms.. There was no difference between the treatment arms in the clinical analysis. Nine patients could be maintained on placebo for 6 weeks, 36 developed mild symptoms and 16 developed severe symptoms. Patients on placebo for 6 weeks had significantly lower serum eotaxin at baseline than patients with symptoms. Patients with mild symptoms had intermediate serum eotaxin concentrations.. Patients with asthma controlled on ICS respond heterogeneously to ICS tapering. Serum eotaxin/CCL11 may be useful in predicting the severity of symptoms patients develop during steroid tapering and should be evaluated in guiding asthma treatment.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Asthma; Biomarkers; Chemokine CCL11; Chemokines, CC; Cytokines; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Respiratory Function Tests; Salmeterol Xinafoate; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome

To investigate the relative efficacy of ciclesonide and fluticasone propionate (FP) administered at comparable microgram doses in maintaining asthma control in patients with moderate-to-severe persistent asthma.. This randomized, open-label, parallel-group study enrolled patients aged 12-75 years with a 6-month history of bronchial asthma. To enter a 2-week run-in period, patients had to have received FP 500-1000 microg/day or equivalent at a stable dose for 4 weeks and have a forced expiratory volume in 1s (FEV 1) 80% of predicted. To enter the treatment period, patients had to have the following during run-in: FEV 1 80% of predicted; reversibility of Delta FEV 1 12% after 200-400 microg salbutamol; and 1 day without asthma symptoms during the last 7 days. Patients were randomized to twice-daily ciclesonide 320 microg (ex-actuator) or twice-daily FP 330 microg (ex-actuator) for 6 months. Efficacy was assessed by lung function, asthma exacerbations, asthma symptoms and rescue medication use. Patients completed the standardized version of the Asthma Quality of Life Questionnaire (AQLQ[S]). Adverse events (AEs), including local oropharyngeal AEs, were recorded.. 528 patients were randomized (ciclesonide, n=255; FP, n=273). In both groups, FEV 1 was maintained from baseline to study end (mean increase: ciclesonide 11 mL, FP 24 mL; intention-to-treat [ITT] analysis). The least squares mean+/-standard error of the mean for the treatment difference was -13+/-29 (95% confidence interval [CI]: -70, 44) in the ITT analysis and -27+/-34 (95% CI: -93, 40) in the per-protocol (PP) analysis, demonstrating non-inferiority of ciclesonide to FP. Morning, evening and site-measured PEF improved significantly with both treatments (ITT and PP analyses: p<0.05). Six patients receiving ciclesonide and seven receiving FP (ITT analysis) experienced an asthma exacerbation requiring treatment with oral corticosteroids. Both treatments significantly decreased asthma symptom score sum (ITT and PP analyses: p0.0001) and rescue medication use (ITT and PP analyses: p<0.05), with no significant difference between treatments. Both treatments significantly improved overall AQLQ(S) score (ITT and PP analyses: p<0.05). Significantly more patients experienced candidiasis and dysphonia with FP compared with ciclesonide (p=0.0023).. Ciclesonide 320 microg and FP 330 microg administered twice daily over 6 months provided similar efficacy in patients with moderate or severe persistent asthma previously well-controlled by high doses of ICS at baseline. Ciclesonide was associated with fewer local AEs than FP.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Quality of Life; Recurrence; Treatment Outcome

Adenosine receptor activation is suggested to play a role in asthmatic airway inflammation. Inhibition of adenosine receptors may have an effect on the late asthmatic response (LAR) after allergen inhalation and this mechanism could offer a potential new treatment in asthma.. We evaluated the effect of an inhaled adenosine-(2A) (A(2A))-receptor agonist (GW328267X), 25 microg, in 15 nonsmoking atopic asthmatics who underwent an inhaled allergen challenge following twice daily treatment for 1 week in a double-blind, placebo- and fluticasone propionate (250 microg) controlled study.. In contrast to fluticasone, treatment with the A(2A)-receptor agonist neither significantly protect against the allergen-induced early and late asthmatic reaction, nor the accompanying inflammatory response as measured by sputum total cell counts, number of EG2+ cells, and the concentration of interleukin-8 and eosinophil cationic protein.. The inhaled A(2A)-receptor agonist, GW328267X, 25 microg does not affect the allergen-induced LAR or the associated inflammatory response in asthma.

Topics: Adenosine A2 Receptor Antagonists; Administration, Inhalation; Adolescent; Adult; Allergens; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchial Provocation Tests; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Fluticasone; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Probability; Reference Values; Respiratory Function Tests; Risk Assessment; Treatment Outcome

Long-term glucocorticoid therapy has been suggested to improve airway and airway vascular smooth muscle responsiveness to inhaled beta(2)-agonists in patients with asthma.. We sought to assess whether a single dose of an inhaled glucocorticoid acutely potentiates beta(2)-adrenergic airway and airway vascular smooth muscle reactivity in asthma.. In 10 asthmatic and 10 healthy subjects, airway blood flow and FEV(1) were measured before and 30 minutes after fluticasone or placebo inhalation and 15 minutes after the subsequent inhalation of racemic albuterol (0.6 mg or 1.25 mg) or (R)-albuterol (0.3 mg or 0.6 mg).. In healthy subjects all albuterol formulations increased airway blood flow equally after placebo or fluticasone pretreatment. In asthmatic subjects airway blood flow response was blunted after placebo and acutely restored after fluticasone pretreatment. Fluticasone pretreatment did not increase FEV(1) responses to any albuterol formulation, except 0.6 mg racemic albuterol.. A single dose of an inhaled glucocorticoid restores beta(2)-adrenergic airway vasodilator responses in patients with mild asthma. The mechanism of this rapid glucocorticoid effect remains to be clarified.

Topics: Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Female; Fluticasone; Humans; Lung; Male; Middle Aged; Muscle, Smooth, Vascular; Placebos; Regional Blood Flow; Respiratory Function Tests

The systemic exposure of fluticasone propionate with hydrofluoroalkane propellant compared with chlorofluoro-carbon propellant and the effect of fluticasone propionate hydrofluoroalkane on 24-hour urinary cortisol in children aged 4 to 11 years with asthma were evaluated. Study 1 was an open-label, 2-way crossover study in which 16 subjects were randomized to 7.5 days each of fluticasone propionate hydrofluoroalkane 88 mug twice a day or fluticasone propionate chlorofluorocarbon 88 mug twice a day. In study 2, 63 subjects received 13.5 days of placebo followed by 27.5 days of fluticasone propionate hydrofluoroalkane 88 mug twice a day. The main outcome measure for study 1 was the difference between fluticasone propionate hydrofluoroalkane and fluticasone propionate chlorofluorocarbon in fluticasone propionate AUC(last) (area under the plasma fluticasone propionate concentration-time curve from zero up to the last quantifiable plasma concentration), and for study 2, 24-hour overnight urinary cortisol excretion. In study 1, fluticasone propionate systemic exposure was significantly lower (55%) with hydrofluoroalkane metered dose inhaler compared with chlorofluorocarbon metered dose inhaler. Study 2 showed no statistically significant changes in 24-hour overnight urinary cortisol excretion and no relationship to fluticasone propionate systemic exposure at this dose. The results of these 2 studies showed that in children aged 4 to 11 years with asthma, fluticasone propionate hydrofluoroalkane has lower systemic exposure compared with chlorofluorocarbon and no hypothalamic-pituitary-adrenal axis effects as measured by 24-hour urinary cortisol excretion.

Topics: Administration, Inhalation; Aerosol Propellants; Androstadienes; Anti-Asthmatic Agents; Area Under Curve; Asthma; Child; Child, Preschool; Chlorofluorocarbons; Cough; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fever; Fluticasone; Half-Life; Headache; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Metered Dose Inhalers; Nausea; Respiratory Tract Infections

The twice daily administration of an inhaled corticosteroid (ICS) and long-acting beta(2)-agonist (LABA) has been shown to be effective in achieving asthma control. The once daily administration of an ICS/LABA may be a treatment option for some patients.. To assess the effectiveness of fluticasone propionate (FP)/salmeterol via a single inhaler (FSC) administered once daily compared with FP once daily, FSC twice daily, or placebo.. A 12-week, randomized, double-blind multicenter study conducted in 844 patients > or = 12 years of age who were symptomatic while using a short-acting beta(2)-agonist alone. Blinded treatments included: FSC 250/50 mcg once daily in the evening (FSC 250/50 QD), FP 250 mcg once daily in the evening (FP 250 QD), FSC 100/50 mcg twice daily (FSC 100/50 mcg BID), or placebo. All treatments were delivered via the Diskus device.. All treatments demonstrated greater improvements in efficacy measures compared with placebo. Overall, the greatest improvements were observed in the patients receiving FSC, either once or twice daily, compared with the FP 250 QD group. The two FSC treatments were similar except that QD dosing did not maintain improvements in lung function for 24h compared with twice daily dosing. All treatments were well tolerated. No suppression of HPA axis, as assessed by 24-h urinary cortisol excretion, was observed in any of the active treatment groups.. In patients symptomatic on a short-acting beta(2)-agonist alone, FSC 100/50 mcg BID was shown to provide better efficacy than a higher strength (FSC 250/50 mcg) administered once daily. However, a once daily regimen was effective and may be a valuable treatment option for some patients. Registered at (http://ctr.gsk.co.uk/welcome.asp) (SAS30022).

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Lung; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate; Safety; Salmeterol Xinafoate; Treatment Outcome

Combined therapy with inhaled corticosteroids (ICSs) and long-acting beta(2)-adrenoceptor agonists (LABAs) is the recommended approach for the treatment of patients with asthma that is uncontrolled on ICSs alone. Additional studies are needed to assess the safety and efficacy of combination treatment with ICSs and LABAs in patients with mild asthma. The aim of this study was to compare the efficacy and tolerability of once-daily salmeterol/fluticasone propionate combination (SFC) with once-daily fluticasone propionate (FP) over a 12-week treatment period in patients with mild persistent asthma.. This was a randomized, double-blind, placebo-controlled, parallel-group, multicentre study carried out in primary care or at a hospital outpatient department and included patients 12-79 years of age with mild persistent asthma (n = 458). After a 2-week run-in period, patients were randomized to receive SFC 50 microg/100 microg (n = 149), FP 100 microg (n = 154) or placebo (n = 155) once daily in the morning for 12 weeks. The primary efficacy endpoint was patient-recorded pre-dose mean morning peak expiratory flow (PEF). Other assessments included asthma symptom scores, use of rescue medication and investigator-recorded exacerbations. Lung function was measured and assessed during clinic visits.. For the primary efficacy endpoint of mean change in morning PEF, SFC achieved significantly greater increases from baseline than both placebo (difference in adjusted means 23 L/min; 95% CI 15.0, 30.3; p < 0.001) and FP (difference in adjusted means 14 L/min; 95% CI 6.3, 21.7; p < 0.001). Compared with those who received FP, patients in the SFC group demonstrated significantly greater improvements in mean evening PEF (95% CI 11.7, 28.1; p < 0.001), forced expiratory volume in 1 second (95% CI 0.093, 0.257; p < 0.001), forced expiratory flow between 25% and 75% of forced vital capacity (95% CI 0.242, 0.617; p < 0.001), the percentage of symptom-free days (95% CI 0.34, 0.87; p = 0.011), and the percentage of rescue medication-free days (95% CI 0.34, 0.90; p = 0.018). During weeks 5-12, 52% of patients in the SFC group achieved 'well controlled' asthma, compared with 42% and 26% of patients in the FP and placebo groups, respectively. Only one patient (receiving placebo) had a severe asthma exacerbation during the study; the frequency of adverse events was similar across the three treatment groups.. Once-daily SFC 50 microg/100 microg provided significantly greater improvements in lung function and in asthma symptoms than once-daily FP 100 microg alone in patients with mild persistent asthma. However, twice-daily treatment with either SFC or ICSs plus short acting beta(2)-adrenoceptor agonists could be required to achieve guideline-defined asthma control in some patients.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Fluticasone; Follow-Up Studies; Forced Expiratory Volume; Humans; Maximal Midexpiratory Flow Rate; Middle Aged; Placebos; Respiratory Function Tests; Salmeterol Xinafoate; Severity of Illness Index; Treatment Outcome

Inhaled corticosteroids (ICS) are preferred drugs for the long-term treatment of all severities of asthma in children. However, data about the safety of ICS in infants is lacking. So, it is essential to do further clinical studies to examine the safety and efficacy of ICS in this population. In this study, the effects of nebulized budesonide and nebulized fluticasone propionate suspensions on hypothalamic-pituitary-adrenal axis is examined in infants with recurrent or persistent wheeze. Thirty-one children aged 6-24 months admitted to our hospital between January and December 2005 with symptoms of recurrent or persistent wheeze were included in the study. The patients were randomly allocated to receive 0.25 mg BUD or 0.25 mg fluticasone propionate twice daily for 6 wk and half dose for another 6 wk with a jet nebulizer at home. Blood samples for basal cortisol concentration, adrenocarticotropic hormone, glucose, HbA1c and electrolytes were obtained at the beginning and at the end of the study. Adrenal function assessment was based on changes in cosyntropin-stimulated plasma cortisol levels. The study was completed with 31 patients, 16 of whom received BUD and 15 FP. All patients except one had plasma cortisol concentrations above 500 nmol/l (18 microg/dl) or had an incremental rise in cortisol of >200 nmol/l after stimulation. Although nebulized steroids seem to be safe in infancy, we recommend that adrenal functions should be tested periodically during long-term treatment with nebulized steroids.

Topics: Administration, Inhalation; Adrenocorticotropic Hormone; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Infant; Male; Nebulizers and Vaporizers; Pituitary-Adrenal System; Recurrence; Respiratory Sounds

The efficacy and safety of twice-daily inhaled salmeterol/fluticasone propionate combination (SFC) therapy have been well established in the treatment of adults and adolescents with asthma. Once-daily administration of SFC could also be appropriate in patients with mild persistent asthma. This study aimed to investigate whether once-daily SFC 50 microg/100 microg was at least as effective as fluticasone propionate (FP) 100 microg twice daily, and more effective than twice-daily placebo, over 52 weeks as initial maintenance therapy in patients with mild persistent asthma.. This was a randomized, double-blind, double-dummy, placebo-controlled, multicentre, parallel-group study carried out in primary and secondary care. Patients aged between 12 and 79 years with a documented clinical history of asthma for > or =6 months who were currently receiving inhaled short-acting beta(2)-adrenoceptor agonists only were enrolled. Patients were randomized to receive either once-daily inhaled SFC 50 microg/100 microg, twice-daily inhaled FP 100 microg (i.e. twice the dose of FP compared with SFC) or placebo for 52 weeks. The primary efficacy endpoints were mean morning peak expiratory flow (PEF), as recorded by patients prior to the use of bronchodilator or study medication, and the rate of investigator-recorded asthma exacerbations.. Patients receiving twice-daily FP and once-daily SFC showed greater improvements in mean morning PEF compared with those receiving placebo (FP, difference in means 20.1 L/min; 95% CI 14.7, 25.5; p < 0.001; SFC, difference in means 14.8 L/min; 95% CI 9.4, 20.2; p < 0.001). The difference in adjusted mean PEF between once-daily SFC and twice-daily FP was -5.3 L/min (95% CI -9.1, -1.6). PEF results showed that once-daily SFC was non-inferior to twice-daily FP. Over 52 weeks, there was a 35% reduction in exacerbation rates with once-daily SFC, which in this respect demonstrated superiority over placebo (p < 0.001). Non-inferiority between once-daily SFC and twice-daily FP with respect to exacerbation rates was not shown. Once-daily SFC significantly improved clinic forced expiratory flow between 25% and 75% of forced vital capacity (difference in means 0.129 L/s; p < 0.001) and clinic PEF (difference in means 10.8 L/min; p < 0.001) compared with twice-daily FP. Both treatments were well tolerated and the safety profile of each was similar to that seen with placebo.. In patients with mild persistent asthma not previously receiving maintenance therapy, once-daily SFC 50 microg/100 microg is an effective treatment compared with placebo, and was non-inferior to twice-daily FP 100 microg with respect to mean morning PEF. However, in this study, once-daily SFC was not as efficacious as twice-daily FP in reducing asthma exacerbation rates. This study confirms the benefits of regular maintenance treatment in patients with mild persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Candidiasis, Oral; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Fluticasone; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Treatment Outcome

For the treatment of bronchial asthma, two types of fluticasone inhaler devices are available, namely, metered-dose inhaler with spacer (MDI-S) and the dry powder inhaler (DPI). The former is recommended for young children with a low peak inspiratory flow (PIF) and the latter for adolescents and adults. But the difference in the therapeutic efficacy between them has been studied only rarely in adolescent patients.. In the present study, 21 post-elementary school-age patients with moderate persistent bronchial asthma (age 8-15 years, 10.3 +/- 2.1 years), who all had a sufficient PIF of 114 +/- 29 L/min, were examined in order to compare the two types of fluticasone inhalers. Eleven of 21 patients inhaled 200 microg/day Flutide using the MDI-S twice daily for 1 month in the first month, and the same dose using the DPI for the next month. The other 10 patients inhaled the opposite regimens. At the end of the each treatment, spirometry was examined.. Measurements done before therapy and then at the end of MDI-S and DPI therapy, respectively, were as follows: forced expiratory volume in 1 s (FEV(1.0)), 72.4 +/- 18.2%, 91.5 +/- 18.2% and 84.1 +/- 16.3% (MDI-S vs DPI, P > 0.040); maximal mid-expiratory flow (MMEF), 62.0 +/- 23.6%, 88.7 +/- 26.5%, 79.3 +/- 33.4% (P > 0.044) and the peak expiratory flow (PEF) was 73.9 +/- 25.0%, 95.6 +/- 32.8%, and 90.5 +/- 29.5%, respectively (n.s.). MDI-S was thus found to be more effective in terms of %FEV(1.0) and in %MMEF.. High therapeutic efficacy was obtained with the use of the MDI-S in fluticasone inhalation for post-elementary school-age patients with sufficient inspiration ability.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Delivery Systems; Fluticasone; Humans; Metered Dose Inhalers; Powders

A novel breath-synchronized, plume-control inhaler (Tempo inhaler) was developed to overcome limitations of a pressurized metered-dose inhaler. This report compared the Tempo inhaler and a commercial inhaler for fine particle distribution and lung deposition of fluticasone propionate. In vitro fine particle distribution was determined using the Andersen Cascade Impactor at inspiration rates of 28.3 and 45L/min. In vivo lung deposition was assessed in a randomized, two-arm, crossover study of (99m)Tc-radiolabeled fluticasone propionate in 12 healthy adult subjects, analyzed by gamma scintigraphy. In vitro: fine particle fractions at 28.3 and 45L/min were 88.6+/-3.6% and 89.2+/-3.0% (Tempo inhaler) versus 40.4+/-4.7% and 43.1+/-4.4% (commercial inhaler). In vivo: lung deposition was 41.5+/-9.8% (Tempo inhaler) versus 13.8+/-7.4% (commercial inhaler) and oropharyngeal deposition was 18.3+/-7.7% (Tempo inhaler) versus 76.8+/-7.1% (commercial inhaler). Variability of lung deposition was reduced from 55% (commercial inhaler) to 24% (Tempo inhaler) of the delivered dose. The Tempo inhaler produced significantly higher fine particle fraction values, reduced oropharyngeal deposition by 75%, and increased whole, central, intermediate, and peripheral lung delivery by more than 200%. Thus, the Tempo inhaler enhances efficient drug delivery to the lungs.

Topics: Administration, Inhalation; Adult; Aerosols; Androstadienes; Asthma; Bronchodilator Agents; Cross-Over Studies; Female; Fluticasone; Humans; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Particle Size; Radionuclide Imaging; Tissue Distribution

To compare the effects of fluticasone and placebo on asthma control in patients with mild asthma.. Adults with FEV1 >80% predicted and reliever use

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Female; Fluticasone; Follow-Up Studies; Humans; Male; Middle Aged; Treatment Outcome

Little is known about the use of biomarkers in guiding treatment decisions in routine asthma management. The objective of this study was to determine whether adding a LABA to an ICS would control bronchial hyperresponsiveness (BHR) at an overall lower dose of ICS when titration of medication was based upon the assessment of routine clinical measures with or without the measurement of BHR.. After a 2-week run-in period, subjects (> or = 12 years) were randomized to one of three treatment groups. Two groups followed a BHR treatment strategy (based on clinical parameters [lung function, asthma symptoms, and bronchodilator use] and BHR) and were treated with either fluticasone propionate/salmeterol (FSC(BHR) group) or fluticasone propionate (FP(BHR) group) (n=156 each). The third group followed a clinical treatment algorithm (based on clinical parameters alone) and were treated with fluticasone propionate (FP(REF) group; n=154). All treatments were administered via Diskus. Treatment doses were adjusted as needed every 8 weeks for 40 weeks according to the subject's derived severity class, which was based on clinical measures of asthma control with or without BHR.. The mean total daily inhaled corticosteroids (ICS) dose during the double-blind treatment period was lower, although not statistically significant, in the FSC(BHR) group compared with the FP(BHR) group (a difference of -42.9 mcg; p=0.07). Compared with the FP(REF) group, the mean total daily ICS dose was higher in the FSC(BHR) group (a difference of 85.2 mcg) and was significantly higher in the FP(BHR) group (a difference of 131.2 mcg, p=0.037).. This study demonstrated that for most subjects, control of BHR was maintained when treatment was directed toward control of clinical parameters. In addition, there was a trend towards control of BHR and clinical measures at a lower dose of ICS when used concurrently with salmeterol.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Area Under Curve; Asthma; Bronchial Hyperreactivity; Bronchoconstrictor Agents; Bronchodilator Agents; Child; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Humans; Latin America; Latvia; Male; Metered Dose Inhalers; Methacholine Chloride; Middle Aged; Patient Selection; Practice Guidelines as Topic; Salmeterol Xinafoate; Treatment Outcome; United States

To compare the respirable dose delivery of the hydrofluroalkane fluticasone propionate (HFA-FP) via an optimally prepared Aerochamber Plus spacer (AP), via a Synchro-Breathe (SB) device, and pMDI Evohaler (EH).. Seventeen mild to moderate asthmatics completed the study using a randomized, double-blind, double-dummy, three way crossover design. Single doses of placebo or HFA-FP 2.0 mg were administered via the EH, AP, and SB devices. The overnight urinary cortisol : creatinine ratio (OUCC) was measured at baseline and after each dose.. Significant suppression of OUCC occurred from baseline with AP and SB but not EH devices (geometric mean fold suppression, 95% CI): AP: 3.18 (2.29, 4.36), P < 0.001; SB: 1.79 (1.31, 2.40), P = 0.001; EH: 1.12 (0.69, 1.44), p = 0.37 (equating to 68%, 45% and 9% falls, respectively). Significant differences in OUCC between devices were as follows: (geometric mean fold difference, 95% CI): AP vs. EH. 2.83 (2.09, 3.82), P < 0.001; AP vs. SB: 1.78 fold (1.21, 2.60), P = 0.003; SB vs. EH: 1.59 (1.09, 2.31), P = 0.013 (equating to 65%, 44% and 37% differences, respectively).. The use of an optimally prepared AP spacer and breath actuated SB device, when compared with pMDI, significantly increased the respirable dose of HFA-FP.

Topics: Adult; Androstadienes; Asthma; Bronchodilator Agents; Creatine; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Inhalation Spacers; Male; Metered Dose Inhalers; Middle Aged

To compare the efficacy and safety of the salmeterol/fluticasone propionate combination product with concurrent sustained release theophylline plus fluticasone propionate in adult Japanese patients with persistent asthma.. Multicentre, randomised, double-blind, double-dummy, parallel-group study.. Three hundred and eighty-three asthmatic patients receiving sustained release theophylline 200-400mg/day entered the study and were randomised to receive either salmeterol/fluticasone propionate combination (SFC) 50microg/250microg+1 placebo tablet, fluticasone propionate 250microg+1 sustained release theophylline 200mg (SR-T+FP), twice daily for 8 weeks.. The adjusted mean change morning peak expiratory flow (PEF) over 8 weeks was 29.8L/min in the SFC group and 16.3L/min in the SR-T+FP group, with a treatment difference of 13.4L/min (p=0.0004). SFC improved evening PEF, FEV1, V50 and V25 at the completion of treatment to a greater extent than SR-T+FP (all p<0.05). A higher percentage of patients on SFC were symptom free (p=0.0286) and rescue free (ns) than those on SR-T+FP. There was not a statistically significant difference between treatments in symptom scores. Both treatments were well tolerated.. The finding that SFC was associated with greater improvements in lung function than SR-T+FP, a commonly employed treatment for asthmatic patients in Japan, suggests that SFC should be the preferred therapeutic option in these patients.

Topics: Administration, Inhalation; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Japan; Male; Middle Aged; Salmeterol Xinafoate; Theophylline; Treatment Outcome

Inhaled corticosteroids (ICSs) are one of the suggested first-line therapies for patients with persistent asthma of moderate severity.. The efficacy and safety of mometasone furoate (MF) 400 microg twice daily (BID) and fluticasone propionate (FP) 500 microg BID administered for 12 weeks via dry powder inhaler (DPI) were compared in a noninferiority trial, in adults with moderate-to-severe persistent asthma. The primary variable was the change from baseline in am peak expiratory flow rate (PEFR). PM PEFR, forced expiratory volume in 1 second (FEV(1)), asthma symptoms, rescue medication use, response to therapy, exacerbation rates, and adverse events were also assessed.. The lower bound of 95% CIs for treatment differences in the primary variable ranged from 2.6% to 5.6% throughout the 12-week study and were within the prespecified noninferiority range. No significant between-group differences were observed in lung function, rescue medication use, response to therapy, exacerbation rates, or adverse events. At most of the weeks assessed, there were no between-group differences in asthma symptoms. Most adverse events were mild-to-moderate.. MF-DPI 400 microg BID was therapeutically equivalent to FP-DPI 500 microg BID in patients with moderate-to-severe persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Female; Fluticasone; Humans; Male; Metered Dose Inhalers; Middle Aged; Mometasone Furoate; Peak Expiratory Flow Rate; Pregnadienediols; Treatment Outcome

Two identically designed, randomized, multicenter, single-dose, crossover studies were conducted in patients aged > or = 18 years with mild to moderate asthma previously treated with inhaled corticosteroids. After 2 weeks on twice-daily budesonide pressurized metered-dose inhaler (pMDI) 160 microg, patients received a randomized sequence of budesonide/formoterol pMDI 80/4.5 microg x 2 inhalations (160/9 microg), fluticasone/salmeterol dry powder inhaler (DPI) 250/50 microg x 1 inhalation, albuterol pMDI 90 microg x 2 inhalations (180 microg), and placebo pMDI (3-to 14-day washout periods). Improvements in forced expiratory volume in 1 second (FEV(1)) at 3 minutes were significantly (p < 0.001) greater after treatment with budesonide/formoterol pMDI compared with fluticasone/salmeterol DPI and similar to that of albuterol pMDI. In addition, significantly (p < 0.001) more patients treated with budesonide/formoterol pMDI achieved a 15% improvement in FEV(1) within 15 minutes compared with patients treated with fluticasone/salmeterol DPI and placebo. Thus, the early bronchodilatory effects of budesonide/formoterol pMDI were greater than with fluticasone/salmeterol DPI.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Salmeterol Xinafoate

This long-term prospective study was conducted in African Americans with persistent asthma to examine the safety and effectiveness of the combination of the inhaled corticosteroid, fluticasone propionate (FP), and the long-acting beta-agonist, salmeterol, compared with FP alone.. This was a randomized, double-blind, parallel group, multi-center trial in adolescent and adult subjects >/=12 years of age symptomatic on a low dose of an inhaled corticosteroid (ICS). The study consisted of a 2-week screening period on low dose ICS; a 4-week open-label FP 250 mcg twice daily (BID) run-in; a 52-week double-blind period (FP/salmeterol [FSC] 100/50 mcg [n=239] or FP 100 mcg [n=236] BID), and a 4-week FP 250 mcg BID run-out period. Annualized exacerbation rate was the primary outcome for comparing the two treatments. Other measures of asthma control included peak expiratory flow, asthma symptoms, and albuterol use. Safety was assessed through adverse events.. Exacerbation rates were not significantly different in those treated with FSC 100/50 mcg (0.449 per year) compared with FP 100 mcg (0.529 per year, p=0.169). When the per-protocol analysis was applied, the rates were 0.465 and 0.769 per year for FSC 100/50 mcg and FP 100 mcg, respectively. Treatment with FSC 100/50 mcg provided statistically greater improvements in lung function measures and nighttime awakenings (p

Topics: Adolescent; Adult; Albuterol; Androstadienes; Asthma; Black or African American; Bronchodilator Agents; Child; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Fluticasone; Humans; Male; Middle Aged; Polypharmacy; Prospective Studies; Salmeterol Xinafoate

To evaluate whether hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) controls eosinophilic inflammation, including that in the distal airways, more effectively than fluticasone propionate (FP) Diskus.. Fifty patients with well-controlled mild to moderate persistent asthma using FP for more than 6 months were randomly assigned to FP and HFA-BDP groups, and the treatment regimens of the two groups were switched twice between FP and HFA-BDP in a double cross-over manner at 3-month intervals after 2-week washout periods. Evidence of eosinophilic inflammation in blood and induced sputum samples was assessed, together with pulmonary function testing and an Asthma-related Quality of Life Questionnaire (AQLQ) survey after each treatment period.. The peripheral blood differential eosinophil count and sputum levels of eosinophil cationic protein (ECP) showed reciprocal changes during the study periods in both groups. The blood differential eosinophil count was significantly lower during the HFA-BDP than during the FP treatment period in both the FP (p = 0.004) and the HFA-BDP (p = 0.020) group. The late-phase induced sputum ECP level was significantly decreased during the HFA-BDP treatment period in both the FP (p = 0.016) and the HFA-BDP group (p = 0.023). The significant elevation of surfactant protein D values in the late-phase sputum observed in both groups indicated that late-phase sputum was obtained mainly from proximal peripheral airways. Both symptom and activity limitation domains of the AQLQ in the HFA-BDP group significantly increased after switching from FP to HFA-BDP. There were no significant changes in pulmonary function indices in either group at any time during the study.. HFA-BDP improved residual eosinophilic inflammation in asthmatic airways, including distal airways, more effectively than FP.

Topics: Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cross-Over Studies; Eosinophil Cationic Protein; Eosinophilia; Female; Fluticasone; Humans; Leukocyte Count; Male; Middle Aged; Quality of Life; Sputum

There have been no previous large, well-designed direct comparisons of the effects of fluticasone propionate (FP) and budesonide (BUD) on growth in children. This randomised, double-blind study compared the effects on growth of FP and BUD in children aged 6-9 years with persistent asthma. Following a 6-month run-in period (without inhaled corticosteroids), patients with normal growth velocity were randomised to 12 months' treatment with FP 100 micro g bd (n=114) or BUD 200 micro g bd (n=119). Growth velocity was determined by stadiometric height measurement. Lung function, asthma symptoms and use of relief medication were also assessed. Annualised mean growth velocity during run-in was comparable in the two groups (FP: 5.9 cm/yr; BUD: 6.0 cm/yr). During the treatment period, adjusted mean growth velocity was significantly higher in the FP than the BUD group (5.5 cm/yr vs 4.6 cm/yr; P<0.001). Asthma control improved similarly in both treatment groups. Bone mineral density and overnight urinary cortisol:creatinine ratios were similar in the two groups. Drug-related adverse events were reported among 3% of FP-treated children, compared with 2% for BUD. In conclusion, this study demonstrates that FP for childhood asthma has significantly less impact on childhood growth velocity than a therapeutically equivalent dose of BUD.

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Double-Blind Method; Female; Fluticasone; Growth; Humans; Hydrocortisone; Male; Regression Analysis; Treatment Outcome

To investigate the long-term effect of oral magnesium supplementation on clinical symptoms, bronchial reactivity, lung function and allergen-induced skin responses in children and adolescents with moderate persistent asthma.. A double-blind randomized parallel placebo-controlled study.. The patients were recruited from the Pediatric Outpatient Clinic, Division of Pulmonology, Allergy and Immunology, and followed at the Center for Investigation in Pediatrics at State University of Campinas Hospital, Brazil. Thirty-seven out of 72 patients met the study criteria. There were no dropouts.. The 37 patients (aged 7-19 years, 19 males) were randomized in two groups: magnesium (n=18, 300 mg/day) and placebo (n=19), during 2 months. Both patient groups received inhaled fluticasone (250 microg twice a day) and salbutamol as needed. The primary outcome was bronchial reactivity evaluated with methacholine challenge test (PC20).. After a follow-up of 2 months, the methacholine PC20 for testing bronchial reactivity has augmented significantly in the magnesium group only. The skin responses to recognized antigens have also decreased in patients treated with magnesium. The forced vital capacity (FVC), the forced expiratory volume at first second (FEV1), the forced expiratory flow at 25-75 and the FEV1/FVC ratio were similar in both groups. The magnesium group presented fewer asthma exacerbations and used less salbutamol compared to the placebo group.. Oral magnesium supplementation helped to reduce bronchial reactivity to methacholine, to diminish their allergen-induced skin responses and to provide better symptom control in pediatric patients with moderate persistent asthma treated with inhaled fluticasone.

Topics: Adolescent; Adult; Albuterol; Androstadienes; Asthma; Brazil; Bronchodilator Agents; Child; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Flow Rates; Forced Expiratory Volume; Humans; Magnesium; Male; Treatment Outcome; Vital Capacity

In the choice of, or switch between, various inhaled corticosteroids (ICS) it is important to know equipotent doses for clinical treatment effects of the alternatives. Various ICS do have different inherent potency. Further, the ICS are delivered from inhalers that may differ markedly in output characteristics and drug delivery to intrapulmonary airways. Therefore, clinical efficacy comparisons must include drug-inhaler comparisons. We estimated the therapeutic potency ratio of the Flixotide Diskus (fluticasone propionate, FP) and the Pulmicort Turbuhaler (budesonide, BUD) in steroid-naive asthma patients, using a dose-reduction technique (FP 500-0 mcg/day, BUD 800-0 mcg/day). The dose defining end point was loss of asthma control in this paper denoted as exacerbation. In total, 282 patients with proven asthma were enrolled in the study, and 103 in the FP group and 98 in the BUD group completed the study per protocol. In total, 80 patients in the FP-group and 79 in the BUD-group experienced a dose defining exacerbation. The exacerbation frequency increased in a dose-dependent way as the dose was titrated down. From these data the potency difference between the present drug inhaler combinations, Flixotide Diskus and Pulmicort Turbuhaler, was calculated to be between 1.50:1 (95% CI 1.10:1-2.05:1) and 1.75:1 (CI 1.26:1-2.43:1) depending on if patients with insufficient steroid-response were excluded from the calculations or not. In these steroid-naïve patients, the potency difference was evident only at low daily doses, below 200 mcg.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Glucocorticoids; Humans; Male; Metered Dose Inhalers; Peak Expiratory Flow Rate; Treatment Outcome

The present study examined the association between guideline-derived asthma control and health-related quality of life, assessed using the Asthma Quality of Life Questionnaire (AQLQ), in patients with uncontrolled asthma whose treatment was directed towards achieving the highest possible level of control. The present randomised, double-blind, parallel-group study compared the efficacy of fluticasone propionate (FP) and salmeterol/fluticasone propionate combination (SFC) in achieving two composite, guideline-derived measures of control: total control (TC) and well-controlled (WC) asthma. Not achieving these levels was classed as not well-controlled (NWC). Doses were augmented until patients achieved TC or reached the maximum dose. This dose was maintained for the remainder of the study. AQLQ was assessed at baseline and at each clinic visit. AQLQ scores improved throughout the study, reaching near-maximal levels in patients achieving TC and WC, and 52-week mean scores in the three control groups were statistically significantly different. Clinically meaningful improvements (mean change from baseline) were: TC group (SFC 1.9, FP 1.8), WC (SFC 1.5, FP 1.5) and NWC (SFC 1.0, FP 0.9). In conclusion, the treatment aimed at controlling asthma improves the health-related quality of life to levels approaching normal. The difference in Asthma Quality of Life Questionnaire scores between total control and well-controlled confirms that patients distinguish even between these high levels of control.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Health Status; Humans; Male; Metered Dose Inhalers; Middle Aged; Quality of Life; Treatment Outcome

Subepithelial hypervascularity and angiogenesis in the airways are part of structural remodelling of the airway wall in asthma, but the effects of inhaled corticosteroids (ICS) on these have not been explored. Increased vascularity in asthma may contribute to a number of functional abnormalities. A study was undertaken to explore angiogenic modulation by ICS and its likely regulation via vascular endothelial growth factor (VEGF), its receptors and the angiopoietins.. A placebo-controlled intervention study with ICS in asthma was performed, examining vascularity, VEGF, its receptors (VEGFR1 and VEGFR2), and angiopoietin-1 (Ang1) to assess which of these factors were changed in the asthmatic airways after ICS treatment. Airway wall biopsy specimens, lavage fluid and cells were obtained from 35 patients with mild asthma randomised to receive ICS or placebo for 3 months, after which bronchoscopic examination and sample collection were repeated. Immunohistochemistry and image analysis were used to obtain quantitative measures of vessels, angiogenic sprouts, VEGF, VEGFR1, VEGFR2 and Ang1 staining in airway biopsy specimens. ELISA was used to assess VEGF concentrations in the lavage fluid.. Vessel, VEGF and sprout staining were decreased after 3 months of ICS treatment. VEGF levels remained unchanged. VEGF receptors and Ang1 staining were not reduced after treatment.. The findings of this study support an effect of ICS in downregulating angiogenic remodelling in the airways in asthma, associated with decreasing VEGF activity within the airway wall. The environment of the airways after treatment with ICS, with changes in the balance between VEGF, its receptors, Ang1 and sprouts, appears to be less angiogenic than in untreated asthma.

Topics: Administration, Inhalation; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchi; Fluticasone; Humans; Metered Dose Inhalers; Middle Aged; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A

More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children.. The Pediatric Asthma Controller Trial (PACT) compared the effectiveness of 3 regimens in achieving asthma control.. A total of 285 children (ages 6-14 years) with mild-moderate persistent asthma on the basis of symptoms, and with FEV(1) >or= 80% predicted and methacholine FEV(1) PC(20) or= 80% predicted, confirming current guideline recommendations.

Topics: Acetates; Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Body Height; Child; Cyclopropanes; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Quinolines; Salmeterol Xinafoate; Sulfides

We conducted a double blind, randomised, placebo-controlled, crossover study evaluating the effects of halving inhaled steroid dosage plus salmeterol, or salmeterol and tiotropium. Eighteen life-long non-smoking severe asthmatics [mean FEV(1) 1.49 l (51%)] were run-in for 4 weeks on HFA-fluticasone propionate 1000 microg daily, and were subsequently randomised to 4 weeks of either (a) HFA-fluticasone propionate 500 microg BD/salmeterol 100 microg BD/HFA-tiotropium bromide18 microg od; or (b) fluticasone propionate 500 microg BD/salmeterol 100 microg BD matched placebo. Measurements of spirometry and body plethysmography were made. Adding salmeterol to half the dose of fluticasone led to a mean improvement (95% CI) vs. baseline in morning PEF of 41.5 (14.0-69.0)l/min [p<0.05]; and RAW of 0.98 (0.14-1.8)cm H(2)O/l/s [p<0.05]. Adding salmeterol/tiotropium produced similar improvements in PEF and RAW, but also improved FEV(1) by 0.17 (0.01-0.32)l [p<0.05]; FVC 0.24 (0.05-0.43)l [p<0.05] and reduced exhaled NO by 2.86 (0.12-5.6)ppb [p<0.05]. RV and TLC were not altered by either treatment; there were no significant changes in symptoms or quality of life compared with baseline. Addition of salmeterol/tiotropium to half the dose of fluticasone afforded small, but significant improvements in pulmonary function. These effects were not associated with commensurate changes in subjective symptoms or quality of life.

Topics: Adult; Aged; Albuterol; Androstadienes; Asthma; Breath Tests; Bronchodilator Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nitric Oxide; Plethysmography, Whole Body; Quality of Life; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome; Vital Capacity

Previous studies on inhaled steroid and long-acting beta2-agonist combination products may not be representative for the asthma and chronic obstructive pulmonary disease (COPD) patients in family practice.. To compare in a group of doctor-diagnosed patients with asthma or COPD, the effects of a lower dose of fluticasone in a combination product with salmeterol with conventional treatment (i.e. a higher dose of fluticasone), both supplemented with as-needed use of a short-acting bronchodilator.. The study was a 12-week multicentre, randomized controlled, double-blind trial. In all, 41 family practices recruited 137 patients diagnosed with asthma and 40 patients diagnosed with COPD. Primary outcome was the forced expiratory volume in 1 second (FEV1) as percentage of predicted. Morning peak expiratory flow (PEF), symptom-free days, health status [Asthma Quality of Life Questionnaire (AQLQ) and St. George's Respiratory Questionnaire (SGRQ)], exacerbations, use of short-acting bronchodilators and adverse events were secondary outcomes.. FEV1% predicted increased 2.6% (SD 8.3) in fluticasone/salmeterol- and 0.01% (SD 6.6) in fluticasone-treated patients (overall: P=0.036, asthma: P=0.025 and COPD: P=0.700). PEF increased in favour of fluticasone/salmeterol in asthma patients only (P=0.016). Fluticasone/salmeterol-treated asthma patients had 1.1 more symptom-free days per week (P=0.044); no such effect was observed for COPD (P=0.769). There were no differences in total AQLQ and SGRQ scores, exacerbations, use of reliever puffs or adverse effects.. In family practice patients diagnosed with asthma, several treatment goals were better achieved with a lower dose of fluticasone and salmeterol in a combination product than with a higher dose of fluticasone. We found no differences between the two approaches for patients with COPD.

Topics: Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Family Practice; Female; Fluticasone; Humans; Male; Middle Aged; Netherlands; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Surveys and Questionnaires

Beclometasone dipropionate (BDP) extrafine is a hydrofluoroalkane-based, chlorofluorocarbon (CFC)-free inhalation aerosol. This study was conducted to determine whether BDP extrafine and CFC-fluticasone proprionate (FP) aerosols were equivalent in terms of efficacy and tolerability in children with symptomatic mild-to-moderate asthma. Male and female patients (aged 5-12 yr) with an asthma diagnosis for > or =3 months, peak expiratory flow (PEF) > or =60% of predicted normal and suboptimal asthma control were randomised to double-blind treatment with BDP extrafine 200 microg day(-1) (n=139) or CFC-FP 200 microg day(-1) (n=141) for up to 18 weeks. After 6 and 12 weeks, study medication was 'stepped down' to 100 and 50 microg day(-1), respectively, if patients had achieved good asthma control. Patients with poor asthma control discontinued from the study and those with intermediate control continued in the study but did not undergo a dose reduction. The estimated treatment difference in morning PEF% predicted at 6 weeks was -1.9% (90% CI -4.9, 1.0). There was a trend towards a greater increase in forced vital capacity (% predicted) in the BDP extrafine group (5.3 versus 0.4%; p=0.084). A 'step-down' in therapy to 100 microg day(-1) was possible in 36% and 42% of patients in the BDP extrafine and CFC-FP groups, respectively, at 6 weeks. Both drugs were well tolerated. BDP extrafine and CFC-FP aerosols were equally effective at improving asthma control in children with mild-to-moderate asthma at the same daily dose.

Topics: Administration, Inhalation; Aerosols; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Quality of Life; Respiratory Mechanics; Treatment Outcome

Allergic rhinitis (AR) and asthma coexist frequently and a dual treatment is recommended by prescribing topical nasal plus oral inhaled corticosteroids. The purpose of this study was to assess the efficacy of a nasally inhaled corticosteroid aiming at concomitant control of AR and asthma. A controlled trial was conducted among 60 patients with AR and asthma, aged 6-18 years, who were randomized into two groups. During 8 weeks, the experimental group (30 patients) received exclusively fluticasone propionate hydrofluoroalkane (FP-HFA) inhaled through the nose (mouth closed) using a large volume spacer attached to a face mask. The comparison group (30 patients) received a nasal spray of isotonic saline plus oral inhalation of FP-HFA through a mouthpiece attached to the same spacer. Clinical scores for AR and asthma, nasal inspiratory peak flow (NIPF), and spirometry were assessed by blinded observers. There was a significant improvement in AR scores and NIPF in the experimental group (P or= 0.20). Prebronchodilator FEV(1) (% predicted value) improved by 10% in both groups, comparing values at inclusion with those obtained at the end of follow up. Our results suggest that nasally inhaled FP-HFA through a spacer may control AR and asthma in children and adolescents. This approach is likely to result in higher compliance, lower costs, and fewer side effects.

Topics: Administration, Inhalation; Administration, Intranasal; Adolescent; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Metered Dose Inhalers; Rhinitis, Allergic, Perennial; Treatment Outcome

Adherence to medication regimens is poor in the management of chronic diseases, including asthma.. To determine whether an audiovisual reminder device improves adherence with inhaled corticosteroid (ICS) therapy in adult asthma.. A randomized open-label parallel group study of 110 adult or adolescent subjects with asthma was undertaken. Subjects were randomized to receive 24 weeks of fluticasone propionate 250 microg, 1 actuation twice daily via a metered dose inhaler (MDI) with or without an audiovisual reminder function (AVRF). All MDIs had electronic covert adherence monitors. The primary outcome variable was adherence, defined as the proportion of medication taken as prescribed over the final 12 weeks of the study. Adherence was also assessed as the proportion of subjects who took >50%, >80%, or >90% of prescribed medication.. The proportion of medication taken in the last 12 weeks was greater in the AVRF group (93%) compared with the control group (74%), with a difference of 18% (95% confidence interval [CI] 10-26%; P < .0001). The proportion of subjects taking >50%, >80%, or >90% of their medication was greater in the AVRF group, with a ratio of proportions adherent of 1.33 (95% CI, 1.10-1.61; P = .003), 2.27 (95% CI, 1.56-3.3; P < .0001), and 3.25 (95% CI, 1.74-6.1%; P < .0001), respectively.. An audiovisual reminder function can significantly improve adherence with ICS therapy in adult asthma.. An audiovisual reminder function has potential to improve adherence with medication regimens across a wide spectrum of diseases, in both research and clinical practice.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Asthma; Audiovisual Aids; Child; Drug Monitoring; Female; Fluticasone; Humans; Male; Metered Dose Inhalers; Middle Aged; Patient Compliance

Nonadherence with asthma therapy is common and may contribute to poor clinical outcomes.. To examine the effect of dosing frequency and mode of delivery of therapy on adherence and clinical outcomes.. We examined adherence in patients with mild persistent asthma (15-85 years) enrolled in a randomized study of montelukast (10 mg once daily) or fluticasone (88 microg, 2 puffs twice daily) during a 12-week double-blind treatment period (DB), followed by a 36-week open-label trial (OL). Adherence was monitored using eDEM for montelukast/placebo and MDILog devices for fluticasone/placebo.. Participants used at least 1 puff of inhaled therapy on 83.3% DB/76.8% OL of days and at least 1 dose of oral therapy on 77.5%/71.4% of days (P < .0001). Subjects used inhaled therapy less than prescribed on 49.5%/57.5% of days, compared with 22.5%/28.6% of days for oral therapy (P < .0001). In the DB, a dose-response relationship was observed with fluticasone and asthma rescue-free days (P = .02) and FEV(1) percent predicted (P < .01) only for patients with FEV(1) < or = 86%. In the OL period, a dose-response relationship was observed with fluticasone and FEV(1) percent predicted (P < .001).. Whereas subjects were more likely to use inhaled fluticasone/placebo at least once a day, subjects were more likely to take once-daily oral montelukast/placebo as prescribed. Clinical outcomes were inconsistently associated with adherence levels.. Patients were less likely to be fully adherent with twice-daily therapy than with once-daily therapy, but most still achieved adequate asthma control.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Cyclopropanes; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Middle Aged; Patient Compliance; Quinolines; Sulfides

Topics: Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Body Height; Child; Double-Blind Method; Female; Fluticasone; Humans; Omalizumab; Twins, Monozygotic

A comparative study was conducted in elderly subjects with mild bronchial asthma to investigate the clinical usefulness of monotherapy with a leukotriene receptor antagonist in comparison to an inhaled corticosteroid. A total of 41 elderly patients aged 65 years or older with mild bronchial asthma, classified as being in severity step 1 and 2, were randomly assigned to the following two treatment groups: a pranlukast (CAS 103177-37-3, Onon) treatment group of 21 patients and an inhaled corticosteroid treatment group of 20 patients. Patients of the former group received pranlukast 450 mg daily and those of the latter group received fluticasone (CAS 90566-53-3) 200 microg daily for eight weeks. In the reference group, one patient was found to suffer from oral candidiasis 4 weeks after the start of the study. Therefore the evaluation was conducted on the remaining 19 participants. The evaluation parameters examined were obtained by keeping an asthma diary, determinations of PEF (peek expiratory flow), use frequency of beta2 stimulants, changes in symptom scores, and medication compliance. Further, measured before and after therapy were the ratio of peripheral blood eosinophils counts, serum ECP (eosinophils cationic protein), ECP levels induced sputum, and forced expiratory volume in one second (FEV1.0). As a result, in the time-course changes of symptoms scores and morning PEF, swift improvement was noted in the pranlukast group. Further, in the variables such as use frequency of beta2 stimulants, serum ECP levels, ECP levels induced sputum, and FEV1.0, an almost comparable level of improvement to the fluticasone group was demonstrated. From the above results, it was deemed that in elderly patients with mild bronchial asthma classified as steps 1 and 2, the pranlukast monotherapy, with superior medication compliance to inhaled therapy, would produce an equivalent level of clinical efficacy to the monotherapy with inhaled corticosteroid (fluticasone 200 microg daily).

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Chromones; Eosinophils; Female; Fluticasone; Humans; Leukotriene Antagonists; Male; Patient Compliance; Peak Expiratory Flow Rate; Sputum

Vascular endothelial growth factor (VEGF) increases microvascular permeability. Recently, considerable attention has been devoted to the physiologic roles of angiopoietin-1 and angiopoietin-2 as regulatory factors of VEGF. This study was designed to examine the roles of angiopoietin-1 and angiopoietin-2 in controlling airway microvascular permeability in asthma.. Levels of these angiogenic factors and airway vascular permeability index were examined in 30 asthmatics and 12 control subjects. After 2-week run-in period, all asthmatics were randomly assigned to receive fluticasone propionate (400 mug/d) or montelukast (10 mg) for 12 weeks.. VEGF, angiopoietin-1, and angiopoietin-2 levels in induced sputum were significantly higher in asthmatics than in control subjects. We found an inverse correlation between angiopoietin-1 level and vascular permeability index in asthmatics, while there was a positive correlation between angiopoietin-2 level and that index. VEGF and angiopoietin-1 levels were significantly decreased after fluticasone therapy, while VEGF and angiopoietin-2 levels were significantly decreased after montelukast therapy. Although VEGF levels after treatment were different between two groups, vascular permeability index in the montelukast group was the same level as that in the fluticasone group. Moreover, improvement in vascular permeability index after fluticasone therapy was inversely correlated with decrease in angiopoietin-1 level, while that after montelukast therapy was positively correlated with decrease in angiopoietin-2 level.. Angiopoietin-1 and angiopoietin-2 play complementary and coordinated roles in regulating microvascular permeability stimulated by VEGF in asthma. Combination of corticosteroids with leukotriene antagonists might effectively improve plasma leakage and provide a new strategy in treating bronchial asthma.

Topics: Acetates; Adult; Androstadienes; Angiopoietin-1; Angiopoietin-2; Asthma; Biomarkers; Bronchi; Bronchodilator Agents; Capillary Permeability; Cyclopropanes; Female; Fluticasone; Follow-Up Studies; Humans; Immunoassay; Male; Microcirculation; Prognosis; Quinolines; Severity of Illness Index; Sputum; Sulfides; Vascular Endothelial Growth Factor A

To compare the effects of once-daily ciclesonide and twice-daily fluticasone propionate in patients with moderate persistent asthma.. Patients aged 12-75 years with moderate bronchial asthma entered a 1-4 week run-in period. For inclusion into the 12-week, randomized, open-label treatment period, patients had to have a forced expiratory volume in 1s (FEV1) of either 60-80% of predicted or 80% of predicted and a defined use of rescue medication and asthma symptoms, depending on previous treatment. Patients received ciclesonide 320 microg once daily (ex-actuator) or fluticasone propionate 200 microg twice daily. Primary efficacy endpoint was change from baseline in FEV1.. In total, 474 patients were randomized. FEV1 increased significantly from baseline with ciclesonide and fluticasone propionate in the intention-to-treat (ITT) and per-protocol (PP) analyses (all p < 0.0001). Treatment difference was -31 mL (95% confidence interval [CI]: -121, 59) in the PP analysis, demonstrating non-inferiority of ciclesonide. Similar findings were seen for other measures of lung function. In the ITT population, asthma symptom scores and rescue medication use decreased with both treatments (all p < 0.0001). Improvement in health-related quality of life (HRQoL) from baseline was significantly greater with ciclesonide than fluticasone (p = 0.005; one-sided). There were no cases of oral candidiasis in patients receiving ciclesonide and nine cases (3.8%) in those receiving fluticasone propionate (p = 0.002; one-sided).. Treatment with once-daily ciclesonide and twice-daily fluticasone propionate resulted in similar improvements in lung function in patients with moderate persistent asthma. Ciclesonide showed significant improvements in oral candidiasis and HRQoL over fluticasone.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Respiratory Function Tests

Asthma is an inflammatory disease of the airways that can lead to impaired arterial blood oxygenation during exercise.. We asked whether treatment of airway inflammation in asthmatic subjects would improve arterial blood gases during whole-body exercise.. By using a double-blind parallel-group design, 19 asthmatic subjects completed treadmill exercise to exhaustion on 2 occasions: (1) before and (2) after 6 weeks' treatment with an inhaled corticosteroid (ICS; n = 9) or placebo (n = 10).. The ICS group had improved resting pulmonary function, decreased exercise-induced bronchospasm, and decreased postexercise sputum histamine during the posttreatment study compared with that during the pretreatment study. In the ICS group exercise Pao(2) was significantly increased after treatment (84.8 to 93.8 mm Hg). Increased alveolar ventilation (arterial Pco(2) decreased from 36.9 to 34.1 mm Hg) accounted for 37% of the increased Pao(2) and improved gas exchange efficiency (alveolar-to-arterial Po(2) difference decreased from 22.5 to 16.3 mm Hg) accounted for the remaining 63% of the increased Pao(2) after treatment. In the ICS group exercise time to exhaustion was increased from 9.9 minutes during the pretreatment study to 14.8 minutes during the posttreatment study.. Treatment of airway inflammation in asthmatic subjects can improve arterial blood oxygenation during exercise by (1) improving airway function, thereby allowing increased alveolar ventilation during exercise, and (2) improving the efficiency of alveolar-to-arterial blood O(2) exchange.. In asthmatic patients ICSs not only attenuate exercise-induced bronchospasm but also improve arterial blood oxygenation during exercise.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Double-Blind Method; Exercise Test; Female; Fluticasone; Humans; Male; Pneumonia; Pulmonary Gas Exchange; Pulmonary Ventilation; Respiratory Mechanics

Sixty-four patients with persistent asthma receiving 200 to 800 microg of fluticasone propionate daily were enrolled in this switchover study. The patients applied a tulobuterol patch 2 mg every 24 hours for 4 weeks followed by inhalation of salmeterol 100 microg bid for 4 weeks. The mean values for morning and evening peak expiratory flow improved significantly compared with baseline during the 4 weeks of tulobuterol patch treatment. Further improvement was seen on switching to salmeterol treatment, which was significant even in the first week, and continued until the final week of the study. Use of salmeterol alone resulted in a significant increase in the percentage of forced expiratory volume in 1 second %FEV1 from baseline, with 51% of patients feeling that the treatment was effective (vs. 37% on tulobuterol). These data suggest that salmeterol can achieve better control in asthmatic patients after switching from using tulobuterol patches.

Topics: Administration, Cutaneous; Administration, Inhalation; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Fluticasone; Forced Expiratory Volume; Humans; Middle Aged; Patient Compliance; Patient Satisfaction; Salmeterol Xinafoate; Terbutaline

Treatment guidelines recommend the use of inhaled corticosteroids in patients with asthma who have persistent symptoms and the "stepping down" of therapy to the minimum needed to maintain control of asthma. Whether patients with asthma that is well controlled with the use of inhaled corticosteroids twice daily can receive a step-down treatment with once-daily montelukast (our primary hypothesis) or once-daily fluticasone propionate plus salmeterol (our secondary hypothesis) has not yet been determined.. We randomly assigned 500 patients with asthma that was well controlled by inhaled fluticasone (100 microg twice daily) to receive continued fluticasone (100 microg twice daily) (169 patients), montelukast (5 or 10 mg each night) (166 patients), or fluticasone (100 microg) plus salmeterol (50 microg) each night (165 patients). Treatment was administered for 16 weeks in a double-blind manner. The primary outcome was the time to treatment failure.. Approximately 20% of patients assigned to receive continued fluticasone or switched to treatment with fluticasone plus salmeterol had treatment failure, as compared with 30.3% of subjects switched to montelukast. The hazard ratio for both comparisons was 1.6 (95% confidence interval, 1.1 to 2.6; P=0.03). The percentage of days on which patients were free of asthma symptoms (78.7 to 85.8%) was similar across the three groups.. Patients with asthma that is well controlled with the use of twice-daily inhaled fluticasone can be switched to once-daily fluticasone plus salmeterol without increased rates of treatment failure. A switch to montelukast results in an increased rate of treatment failure and decreased asthma control; however, patients taking montelukast remained free of symptoms on 78.7% of treatment days. (ClinicalTrials.gov number, NCT00156819 [ClinicalTrials.gov].).

Topics: Acetates; Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Cyclopropanes; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Kaplan-Meier Estimate; Male; Peak Expiratory Flow Rate; Quinolines; Salmeterol Xinafoate; Sulfides; Treatment Failure; Vital Capacity

Asthma is generally accepted as an inflammatory disease that needs steroid treatment. However, when to start with inhaled steroids remains unclear. A study was undertaken to determine when inhaled corticosteroids should be introduced as the first treatment step.. To investigate the effectiveness of early introduction of inhaled steroids on decline in lung function in steroid-naïve subjects with a rapid decline in lung function in general practice.. Patients with signs/symptoms suspect of asthma (i.e., persistent and/or recurrent respiratory symptoms) and a decline in forced expiratory volume in 1 s (FEV(1)) during 1-year monitoring of 0.080 l or more and reversible obstruction (> or =10% predicted) or bronchial hyperresponsiveness (PC(20)< or =8 mg/ml) were studied. They had been identified in a population screening aiming to detect subjects at risk for chronic obstructive pulmonary disease (COPD) or asthma.. A placebo-controlled, randomized, double-blind study.. 75 subjects out of a random population of 1155 were found eligible, and 45 were willingly to participate. Subjects were randomly treated with placebo or fluticasone propionate 250 microg b.i.d., and FEV(1) and PC(20) were monitored over a 2-year period.. The primary outcome measure was decline in FEV(1); the secondary outcome measure was bronchial hyperresponsiveness (PC(20)).. 22 subjects were randomly allocated to the active group with inhaled corticosteroids and 23 to placebo. Change of FEV(1) in the active treated group was +43 ml in post-bronchodilator FEV(1) (p =0.341) and +62 ml/year (p =0.237) in pre-bronchodilator FEV(1) after 1 year, and -22 ml (p =0.304) for post-bronchodilator FEV(1) and -9.4 ml (p =0.691) for pre-bronchodilator FEV(1) after 2 years, compared to placebo. The effect on PC(20) was almost one dose-step (p =0.627) after 1 year and one dose-step (p =0.989) after 2 years.. In this study, the early introduction of inhaled corticosteroids in newly diagnosed asthmatic subjects with rapid decline in lung function did not prove to be either clinically relevant or statistically significant in reversing the decline in FEV(1). For PC(20), no significant changes were detected.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Humans; Lung; Netherlands; Placebos; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

Management plans for childhood asthma show limited success in optimising asthma control. The aim of the present study was to assess whether a treatment strategy guided by airway hyperresponsiveness (AHR) increased the number of symptom-free days and improved lung function in asthmatic children, compared with a symptom-driven reference strategy. In a multicentre, double-blind, parallel-group, randomised, 2-yr intervention trial, 210 children (aged 6-16 yrs) with moderate atopic asthma, selected on the basis of symptom scores and/or the presence of AHR, were studied. At 3-monthly visits, symptom scores, forced expiratory volume in one second (FEV(1)) and methacholine challenge results were obtained, and medication (five levels of fluticasone with or without salmeterol) adjusted according to algorithms based on symptom score (reference strategy, n = 104) or AHR and symptom score (AHR strategy, n = 102). After 2 yrs, no difference was found in the percentage of symptom-free days between treatment strategies. Pre-bronchodilator FEV(1) was higher in the AHR strategy (2.3% predicted). This was entirely explained by a gradual worsening of FEV(1) in a subgroup of 91 hyperresponsive children enrolled with low symptom scores (final difference between study arms was 6%). Asthma treatment guided by airway hyperresponsiveness showed no benefits in terms of number of symptom-free days, but produced a better outcome in terms of pre-bronchodilator forced expiratory volume in one second in allergic asthmatic children, especially those characterised by low symptom scores despite airway hyperresponsiveness.

Topics: Administration, Inhalation; Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Salmeterol Xinafoate; Treatment Outcome

The effect of inhaled steroids on oxidative stress in asthmatics is unclear. The levels of lipid peroxides in the serum of asthmatic patients, whose symptoms were controlled with inhaled corticosteroids and long-acting beta(2)-agonists, were measured in this study.. Twenty asthmatic patients and 17 matched, healthy controls were recruited. Oxidative stress levels were quantified by measuring thiobarbituric acid reactive substances.. After 3 months of treatment, the mean lipid peroxide concentrations were significantly higher in asthmatic patients than in the healthy controls (4.2 +/- 0.13 micromol/mL vs. 3.6 +/- 0.07 micromol/mL, respectively).. The level of lipid peroxides is higher in patients with asthma than in healthy controls, even when the asthma is well controlled after 3 months of treatment. A longer period of therapy may be required before lipid peroxidation normalizes.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Lipid Peroxides; Male; Middle Aged; Oxidative Stress; Reactive Oxygen Species; Salmeterol Xinafoate; Thiobarbituric Acid Reactive Substances

To investigate the magnitude of change in morning peak expiratory flow (PEF), asthma symptoms, and rescue beta2-agonist use, when the aim of treatment is to achieve guideline-defined control.. This was a protocol-defined analysis of data from the previously-reported one-year, stratified, randomised, double-blind, parallel-group GOAL study comparing the use of salmeterol/fluticasone propionate with fluticasone propionate alone in achieving guideline-defined control; this analysis assessed the magnitude of change in single specific endpoints which were amalgamated into the composite measure of control used in the primary GOAL analysis.. Across all strata, improvements were seen for each outcome at 52 weeks as compared to baseline: mean morning PEF, 58.2 l/min (salmeterol/fluticasone propionate) versus 33.9 l/min (fluticasone propionate alone); symptom scores, -1.0 versus -0.8; symptom-free days, 72.5% versus 54.5%; mean of zero night awakenings, 31% versus 22%; rescue-free days, 87.3 versus 74.7; annualised rate of severe exacerbations, 0.02 versus 0.03; p<0.001 for all treatment differences.. Aiming for guideline-defined control resulted in sustained, clinically relevant improvements in a range of individual asthma outcomes. Improvements were greatest with salmeterol/fluticasone propionate versus fluticasone propionate alone.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Combinations; Endpoint Determination; Female; Fluticasone; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Treatment Outcome

Improving patients' health-related quality of life (HRQoL) is recognized as a fundamental part of asthma management. The aims of this study were to evaluate the long-term efficacy (including symptom-free days and exacerbations) and impact on HRQoL of a stable-dose regimen of salmeterol/fluticasone propionate (SAL/FP) and an adjustable maintenance dosing (AMD) regimen of formoterol/budesonide (FOR/BUD) where treatment is adjusted based on symptoms [SAM40056].. A total of 688 outpatients with asthma receiving regular low-dose inhaled corticosteroids (ICS) plus a long-acting beta2-agonist, or medium dose ICS alone participated in this randomized, double-blind, double-dummy, parallel-group, 1-year trial, which was conducted in 91 centers in 15 countries. Patients were randomized to receive 1 inhalation of SAL/FP 50/250 mug BID or 2 inhalations of FOR/BUD 6/200 mug BID during Weeks 1-4. For Weeks 5-52, patients meeting strict continuation criteria for stable asthma at Week 4 received AMD with FOR/BUD or stable-dose SAL/FP.. The percentage of symptom-free days was significantly greater (58.8% vs 52.1%; p = 0.034) and the annual exacerbation rate was significantly lower (47%; p = 0.008) with stable-dose SAL/FP compared with FOR/BUD AMD. A total of 568 patients completed the Asthma Quality of Life Questionnaire (AQLQ) at least once during the study. The mean change from baseline in AQLQ overall score was numerically greater with SAL/FP than FOR/BUD at week 28 and week 52, but did not reach statistical significance (p = 0.121 at Week 52). However, in a post hoc logistic regression analyses for any AQLQ improvement, significant benefits with SAL/FP were seen at both time points (p = 0.038 and p = 0.009, respectively). The minimally important difference of >/= 0.5-point improvement in AQLQ overall score was achieved by a significantly greater number of patients receiving SAL/FP at Week 28 (68% vs 60%; p = 0.049); a trend for this difference remained at Week 52 (71% vs 65%) (p = 0.205).. In this population of patients with persistent asthma, stable-dose SAL/FP resulted in significantly greater increases in symptom-free days, a reduction in exacerbation rates, and provided greater HRQoL benefits compared with FOR/BUD AMD.. Clinical Trials registration number NCT00479739.

Topics: Administration, Inhalation; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Quality of Life; Salmeterol Xinafoate; Treatment Outcome

It is important to evaluate the effects of hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP), which shows predominant deposition in the lower airways, on asthmatic inflammation in the lower airways and the Quality of Life (QOL) of asthma patients, as compared with those of fluticasone propionate (FP) Diskus.. Seventy-seven adult patients with mild persistent or more severe asthma who were being treated with FP for >/=3 months were randomly assigned to the HFA-BDP group and continued FP group. The differential count of eosinophils in the peripheral blood, the serum cortisol levels, and pulmonary function parameters were measured before the study and at 3 months after the start of the study treatment. The improvements in the Asthma Quality of Life Questionnaire (AQLQ) scores were also compared. Sputum samples collected by the induced expectoration method (inhalation of 10% saline for 15 min) were divided into the early-phase sputum samples obtained within 15 minutes of the inhalation and the late-phase sputum samples obtained later than 15 minutes after the inhalation, and the eosinophil count and eosinophil cationic protein (ECP) levels were measured.. In the HFA-BDP group (N=40), the differential count of eosinophils in the peripheral blood was significantly decreased as compared with that in the FP group (p=0.009), and the scores in all the domains of the AQLQ and the percentage improvement of the total score were significantly better as compared with those in FP group (p=0.033). The eosinophil count in the late-phase sputum samples (p=0.022) as well as the ECP level in the sputum samples showed more pronounced decreases in the HFA-BDP group as compared with those in the FP group. On the other hand, no significant changes were detected in the pulmonary function values.. Use of the HFA-BDP preparation can more effectively suppress residual inflammation in the lower airways and significantly improve the QOL as compared with use of the FP preparation of asthma patients. Examination of induced sputum samples allows detection of changes in the peripheral airways that cannot be detected by pulmonary function testing.

Topics: Administration, Inhalation; Aerosol Propellants; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Middle Aged; Quality of Life

This study compared the effect of inhaled fluticasone propionate (FP) with the combination of salmeterol/fluticasone propionate (SFC) on lung function parameters in patients with mild asthma.. Adult patients with mild persistent asthma (> or = 80% predicted FEV1) receiving 200-500 mug of BDP or equivalent were randomised to receive either FP 100 mug or SFC 50/100 mug twice daily from a Diskus inhaler for four weeks. The primary outcome was the change from baseline in airway resistance (sRaw) at 12 hrs post dose measured by whole body plethysmography. Impulse oscillometry and spirometry were also performed.. A comparison of the geometric mean sRaw at 12 hrs post dose in the SFC group to the FP group gave a ratio of 0.76 (0.66 - 0.89, p < 0.001) at week 2 and 0.81 (0.71 - 0.94, p = 0.006) at week 4. Similarly, significant results in favour of SFC for oscillometry measurements of resistance and reactance were observed. FEV1 was also significantly superior at week 2 in the SFC group (mean difference 0.16L, 95% CI; 0.03 - 0.28, p = 0.015), but not at week 4 (mean difference 0.17L, 95% CI -0.01 - 0.34, p = 0.060).. SFC is superior to FP in reducing airway resistance in mild asthmatics with near normal FEV1 values. This study provides evidence that changes in pulmonary function in patients with mild asthma are detected more sensitively by plethysmography compared to spirometry. NCT00370591.

Topics: Adult; Albuterol; Androstadienes; Asthma; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Respiratory Function Tests; Respiratory Physiological Phenomena

To identify the asthma patients, on short-acting beta2-agonists alone, who would benefit from initial maintenance therapy (IMT) with salmeterol/fluticasone (SFC) propionate 50/100 microg bd compared with fluticasone propionate (FP) 100 microg bd alone. The results of an integrated analysis of data from four previous trials are presented.. The four original trials were randomised, double-blind, parallel group studies and included patients who had received IMT with SFC 50/100 microg bd or FP 100 microg bd. Patients were >or=12 years with a 6 month history of asthma and >or=15% reversibility in FEV1. Patients had either not received inhaled corticosteroids in the preceding month or were steroid naïve. Patients were assessed to determine whether any GINA-defined asthma characteristics or combination of asthma characteristics could predict those individuals who would achieve well controlled asthma status with IMT with SFC rather than with inhaled steroid alone. Patients with persistent asthma were assessed based on GINA-defined baseline asthma characteristics and well controlled asthma status in response to each treatment was investigated according to combinations of these baseline features. Subsequently, a further range of endpoints, including asthma symptoms, rescue medication use and asthma control, were analysed over weeks 1-12 for the combinations of features where the treatment difference in well controlled asthma status was greatest.. The results of the initial analyses demonstrated that patients exhibiting two or three features of uncontrolled asthma at baseline were more likely to achieve well controlled asthma when treated with SFC than with FP alone, the most significant difference being observed in patients with three baseline features (odds ratio 2.60, 95% CI: 1.87, 3.62, p<0.001). Patients with one baseline feature showed no difference between the FP and SFC groups. Further analyses on data from patients with two or three baseline asthma features, showed that treatment with SFC resulted in significantly greater improvements in mean morning PEF, percentage symptom-free days, nights with no awakenings and rescue-free days compared with FP. In addition, asthma control was achieved earlier in patients in the SFC group. SFC and FP were well tolerated as shown previously in the four individual trials.. Patients on short-acting beta2-agonists alone with two or three features of uncontrolled asthma (moderate to severe airflow limitation/daily symptoms/daily rescue medication use) are most likely to achieve better control, earlier, with SFC 50/100 microg bd initial maintenance treatment compared with FP 100 microg bd alone.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Patient Selection; Peak Expiratory Flow Rate

The objective of the present study was to investigate the kinetics of high doses of inhaled steroid fluticasone in comparison with oral steroid prednisone on plasma protein leakage and bronchial eosinophilia in adults with moderate asthma exacerbations. The study design was a randomised, double-blind, placebo-controlled prospective trial. In total, 45 patients treated at the emergency department for moderate asthma exacerbations were recruited and 39 were assigned to receive fluticasone and placebo of prednisone (19 patients), or prednisone and placebo of fluticasone (20 patients). Medication was administered to all patients via a metered-dose inhaler and spacer (16 puffs; 4,000 microg.day(-1) or placebo) plus one pill (prednisone 30 mg.day(-1) or placebo). Spirometry and induced sputum for differential cell counts, albumin and alpha(2)-macroglobulin levels and blood eosinophils, interleukin-5 and granulocyte-macrophage colony-stimulating factor levels were obtained before treatment and at 2, 6 and 24 h after treatment. Symptoms clearly improved after 24 h in both groups. No differences were seen between groups in peak expiratory flow or forced expiratory flow in one second, which improved progressively but then decayed slightly after 24 h. Eosinophil counts in sputum also improved over time in both groups. The effect was faster with fluticasone than with prednisone, but was partially lost at 24 h. However, plasma proteins in sputum and eosinophil count in blood both decreased until 24 h, with no significant differences between groups. There was no correlation between eosinophil counts and plasmatic protein levels. In conclusion, both treatments improved symptoms, airway obstruction and inflammation, and plasma protein leakage at 24 h. Prednisone reduced blood eosinophil counts, while fluticasone reduced airway eosinophil counts, suggesting that the anti-inflammatory performance of fluticasone is exerted locally.

Topics: Administration, Inhalation; Administration, Oral; Adult; Aged; Albumins; Androstadienes; Anthropometry; Anti-Inflammatory Agents; Asthma; Blood Cell Count; Blood Proteins; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Humans; Interleukins; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate; Prednisone; Pulmonary Ventilation; Spirometry; Sputum

To determine whether and to what extent bronchoconstriction affects plasma concentrations of fluticasone and budesonide following inhalation.. Twenty people with mild asthma inhaled 1000 microg fluticasone (Accuhaler) plus 800 microg budesonide (Turbohaler) on two visits. On one occasion, prior to drug inhalation, FEV(1) was decreased by at least 25% using inhaled methacholine. Plasma drug concentrations were measured for each drug over 5 h and area under the plasma concentration-time curve (AUC(0,5 h)) compared between visits.. The mean difference in FEV(1) prior to drug inhalation on the 2 days was 33%. AUC(0,5 h) values for fluticasone and budesonide were lower by a median of 60% (IQR 36-75) and 29% (IQR 2-44), respectively, when administered following bronchoconstriction; the reduction was greater for fluticasone than for budesonide, P = 0.007.. The lower plasma concentrations of fluticasone and, to a lesser extent, budesonide seen when the drugs were inhaled following induced bronchoconstriction, is likely to reflect variations that will occur with fluctuations in airway caliber in asthma.

Topics: Administration, Inhalation; Adult; Aged; Androstadienes; Asthma; Bronchoconstriction; Bronchodilator Agents; Budesonide; Cross-Over Studies; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Treatment Outcome

To compare a step-down approach in well-controlled asthma patients, as recommended by treatment guidelines, from fluticasone propionate 250 microg twice daily (FP250 BID), or equivalent, to ciclesonide 160 microg once daily (CIC160 OD) with continued FP250 BID treatment.. Patients with well-controlled asthma prior to study entry were included in two identical, randomized, double-blind, double-dummy, parallel-group studies. After a 2-week run-in period with FP250 BID, patients were randomized to CIC160 OD (n = 58) or FP250 BID (n = 53) for 12 weeks. Primary endpoints were percentage of days with asthma control, asthma symptom-free days, rescue medication-free days and nocturnal awakening-free days. Secondary endpoints included lung function variables, asthma symptom scores, rescue medication use and asthma exacerbations. Safety variables were also recorded.. Patients had >or= 97% of days with asthma control, 98% asthma symptom-free days and 100% of days free from rescue medication use and nocturnal awakenings in both treatment groups (median values). There were no significant between-treatment differences for any of the primary or secondary efficacy variables. Overall, 42 treatment-emergent adverse events (TEAEs) were reported in the CIC160 OD group and 49 TEAEs were reported in the FP250 BID group. There were no clinically relevant changes from baseline in the safety variables in either treatment group.. Patients well controlled on FP250 BID, or equivalent, who were stepped down to CIC160 OD, maintained similar asthma control compared with patients who received continued treatment standardized to FP250 BID.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Middle Aged; Pregnenediones; Treatment Outcome

Recommended treatment for moderate to severe asthma is the combination of an inhaled corticosteroid and a long-acting beta(2)-agonist. The present study was designed to compare a new fixed combination of extrafine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol.. This was a phase III, multinational, multicentre, double-blind, randomized, two-arm parallel groups, controlled study. After a 2-week run-in period, 228 patients with moderate to severe asthma were randomized to a 12-week treatment with either beclomethasone 100 microg plus formoterol 6 microg or fluticasone 125 microg plus salmeterol 25 microg, both delivered two inhalations b.i.d. via a pressurized metered dose inhaler.. The analysis of noninferiority on the primary outcome, morning peak expiratory flow in the last 2 weeks of treatment, showed no difference between groups (difference -3.32 l/min; 95% CI -17.92 to 11.28). A significant improvement from baseline in lung function, symptom score and rescue medication use was observed in both groups at all time points. Beclomethasone plus formoterol combination showed a significantly faster onset of bronchodilation when compared with fluticasone plus salmeterol with the difference maintained for up to 1 h postdosing. No differences were observed between treatments in the rate of asthma exacerbations, frequency of adverse events and overnight urinary cortisol/creatinine ratio.. The new combination of extrafine beclomethasone plus formoterol is not inferior to the marketed combination of fluticasone and salmeterol in terms of efficacy and tolerability, with the advantage of a faster onset of bronchodilation. ( ClinicalTrials.gov number, NCT00394368).

Topics: Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Severity of Illness Index; Time Factors

This 12-week, double-blind, parallel-group study compared the efficacy and safety of once daily ciclesonide and twice daily fluticasone propionate in patients aged 12-75 years with persistent asthma. Patients were randomized to once-daily ciclesonide 80 micro g (n = 278) or 160 micro g (n = 271), or twice daily fluticasone propionate 88 micro g (n = 259) (all ex-actuator). Significant improvements from baseline were seen in all three treatment groups for forced expiratory volume in 1 second, asthma symptom scores and rescue medication use (all p < 0.0001). Asthma exacerbation rates were low (each ciclesonide group, n = 2; fluticasone group, n = 1). Adverse event reporting indicated good tolerability. Once daily ciclesonide 80 micro g or 160 micro g showed comparable efficacy and tolerability to twice daily fluticasone propionate 88 micro g in persistent asthma.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Asthma; Child; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Middle Aged; Pregnenediones; Respiratory Function Tests

Few studies have compared treatment strategies in patients with asthma poorly controlled on low dose inhaled corticosteroids, and little is known about the effects of different treatments on airway inflammation. In this double-blind, placebo-controlled, parallel group study, we compared the effects of salmeterol plus fluticasone propionate (FP) (Seretide; SFC) and FP plus montelukast (FP/M) on sputum inflammatory markers, airway responsiveness, lung function, and symptoms in adult asthmatics.. Sixty-six subjects were randomised to SFC or FP/M for 12 weeks. The primary outcome was changes in neutrophil, eosinophil, macrophage, lymphocyte, and epithelial cell levels in induced sputum. Additional outcomes included the change in other sputum markers of airway inflammation, airway responsiveness, symptom control, and lung function.. Both treatments had no significant effect on induced sputum inflammatory cells, although there was a trend for a reduction in sputum eosinophils. Both treatments significantly improved airway responsiveness, whereas SFC generally led to greater improvements in symptom control and lung function than FP/M. FP/M led to significantly greater reductions in sputum cysteinyl leukotrienes than SFC (treatment ratio 1.80; 95% CI 1.09, 2.94).. Both treatments led to similar control of eosinophilic airway inflammation, although PEF and symptom control were better with SFC. STUDY NUMBER: SAM40030 (SOLTA).

Topics: Acetates; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Cyclopropanes; Cysteine; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Histamine; Humans; Interleukin-8; Leukotriene Antagonists; Leukotrienes; Lung; Male; Quinolines; Spirometry; Sputum; Sulfides; Time Factors; Treatment Outcome; United Kingdom

Relapses of asthma following emergency department discharge can be reduced with oral and inhaled corticosteroids (ICSs), but the benefits of long-acting beta-agonists (LABAs) are unclear.. To determine whether the addition of a LABA reduces relapses in patients with acute asthma.. This was a randomized, controlled, double-blind trial of 137 patients, aged 18-55 years, conducted in four Canadian EDs. Patients receiving high-dose ICSs or oral corticosteroids, and those who were medically unstable, were excluded. Patients were randomized to either fluticasone 1,000 microg/day with salmeterol 100 microg/day or fluticasone 1,000 microg/day alone. All patients were discharged on seven days of oral prednisone. The main outcome measure was relapse at 21 days.. Both groups had similar baseline characteristics. After 21 days, seven of 69 patients (10.1%) treated with fluticasone/salmeterol and ten of 68 patients (14.7%) treated with fluticasone experienced a relapse (p = 0.42). Prior intubation, female gender, and prior use of ICSs were associated with relapse. There were no clinically or statistically significant differences in overall quality of life and individual domain scores. Fluticasone/salmeterol improved quality of life (p < 0.05) and relapses (24% to 13%; p = 0.35) in patients receiving ICSs at the time of emergency admission.. Outpatient treatment with a short course of systemic corticosteroids combined with ICSs is adequate for most patients with asthma discharged from the emergency department; those already receiving ICS agents may benefit from ICS/LABA combination therapy to improve quality of life. Larger studies are needed to confirm the role of inhaled LABAs in acute asthma.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Therapy, Combination; Emergency Service, Hospital; Female; Fluticasone; Humans; Male; Middle Aged; Patient Discharge; Prednisone; Quality of Life; Recurrence; Respiratory Function Tests; Salmeterol Xinafoate; Treatment Outcome

The effect of ethnicity on the efficacy of salmeterol (S)+fluticasone propionate (FP) has not been examined in Japanese and Caucasian asthmatics. In this study, the efficacy of combination treatment with S and FP from a single inhaler (SFC) was compared with concurrent treatment with S and FP administration from separate inhalers (S+FP) in Japanese and Caucasian asthmatics.. This was a randomised, double-blind, crossover study in male and female Japanese (n=18) and Caucasian (n=17) asthmatics (50-100% predicted FEV(1); >35% reversibility in sGaw). Subjects received SFC (S 50 mcg/FP 250 mcg b.i.d.) and S+FP (S 50 mcg b.i.d.+FP 250 mcg b.i.d.) for 14 days. sGaw and FEV(1) were determined 0-12h after the first and last doses.. Treatment with both SFC and S+FP produced marked bronchodilation, which was maintained 0-12h after the first dose. Baseline sGaw and FEV(1) increased up to 51% and 180 mL, respectively, in Japanese subjects over 2 weeks of treatment, with similar improvements in Caucasian subjects. On Day 14 the 0-12h S+FP:SFC treatment ratios (90% CI) for sGaw AUC and peak were 1.05 (0.98, 1.12) and 1.05 (0.97, 1.14), respectively, in Japanese subjects, and 0.99 (0.92, 1.07) and 0.98 (0.89, 1.07), respectively, in Caucasian subjects, with no difference between the two ethnic groups.. The finding of a similar significant bronchodilator response in Japanese and Caucasian asthmatics following concurrent and combination treatment with salmeterol and FP suggests that the therapeutic response to these agents is comparable and independent of ethnicity in Japanese and Caucasian asthma patients.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Airway Resistance; Albuterol; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Asian People; Asthma; Body Height; Cross-Over Studies; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Japan; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Respiratory Function Tests; Salmeterol Xinafoate; Sweden; Treatment Outcome; White People

During the Gaining Optimal Asthma controL study, 3416 patients with uncontrolled asthma were randomized to receive salmeterol/fluticasone propionate combination (SFC) or fluticasone propionate (FP) for 1 year. Approximately two thirds of patients achieved well-controlled (WC) asthma, and one third continued to have asthma that was not well controlled (NWC).. This analysis aimed to (1) identify factors influencing treatment response and (2) assess the clinical benefits of SFC and FP in patients with NWC asthma.. Logistic regression analysis was used to investigate whether covariates influenced the achievement of at least WC asthma in the study population. In patients with NWC asthma, predefined criteria were used to assess improvements in 6 clinical outcomes.. Factors affecting the probability of having NWC asthma included smoking status (current vs never: odds ratio [OR], 2.757; 95% CI, 2.061-3.689; P < .0001; former vs never: OR, 1.274; 95% CI, 1.031-1.574; P = 0.0273), sex (women vs men: OR, 0.652; 95% CI, 0.527-0.806; P < .0001), history of inhaled corticosteroid use (no history vs history: OR, 0.546; 95% CI, 0.437-0.683; P < .0001), and treatment (FP vs SFC: OR, 1.972; 95% CI, 1.686-2.308; P < .0001). Of patients with NWC asthma, 86% to 96% showed improvements in 1 or more clinical outcomes.. It is imperative for good asthma control that patients stop smoking. Patients who did not have at least WC asthma demonstrated clinical improvements in individual asthma outcomes.. Although not all patients can achieve guideline-defined control, long-term treatment with SFC or FP is associated with clinical improvements in nearly all patients, regardless of smoking history or inhaled corticosteroid use.

Topics: Adrenergic beta-Agonists; Adult; Age Factors; Aged; Albuterol; Androstadienes; Anti-Allergic Agents; Asthma; Body Height; Bronchodilator Agents; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Salmeterol Xinafoate; Sex Factors; Smoking

Using a composite measure based on clinical outcomes, the GOAL study showed that achievement of Total Control of asthma was time dependent with the proportion of controlled patients continuing to rise through the year-long study. Taking data from this study, we compared time taken to achieve Total Control with time taken to achieve total control of each individual clinical criterion on treatment with salmeterol/fluticasone propionate (SFC) or fluticasone propionate (FP) alone.. Time to achieving total control of individual outcomes (day-time symptoms, night-time awakenings, rescue medication use, PEF > or =80% predicted every day) were analyzed by Kaplan Meier plots and compared with achievement of composite Total Control.. Night-time awakenings responded most rapidly and daytime symptoms took longest to respond. After 12 weeks, the proportion of patients who achieved control of any individual clinical criterion was higher than the proportion who achieved control when using the composite outcome (no night-time awakenings achieved by 73% with SFC and 65% with FP; PEF > or =80% predicted every day, 55% and 45% respectively; no rescue usage 46% and 35% respectively; and no daytime symptoms, 35% and 24% respectively, compared with Total Control, 23% and 14% respectively). In every measure except night-time awakenings, more rapid responses were seen for SFC compared with FP alone.. Speed of response of individual asthma measures varies and evaluation of control using any single measure overestimates total asthma control. Treatment should be continued until composite control is reached, rather than control of individual outcomes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Drug Therapy, Combination; Female; Fluticasone; Humans; Individuality; Male; Middle Aged; Peak Expiratory Flow Rate; Quality of Life

To monitor the changes of symptom scores, airway hyperresponsiveness (AHR, represented by PC(35) sGaw), FEV(1)% and PEF% in patients with mild and moderate persistent asthma who received combined therapy of inhaled corticosteroids (ICS) and long-acting beta(2) agonists (LABA) and to evaluate the clinical significance of PC(35) sGaw and other parameters in guiding the adjustment of asthma stepwise therapy.. Patients with asthma were allocated randomly to group A (22 subjects), B (22 subjects), and C (21 subjects). The initial regimens for all patients in the first three months included ICS (fluticasone) plus LABA (salmeterol). For patients in group A, a fixed dosage was maintained for 18 months, while those in group B received tailored dosage or withdrawal of therapy according to the clinical control level (well or total control). The regimens for patients in group C included step-down or withdrawal according to PC(35) sGaw besides the clinical control. All subjects were followed-up for 18 months and the symptom scores, PC(35) sGaw, FEV(1)% and PEF% were measured and analyzed. The asthma clinical control levels of the three groups at end point were compared.. A total of 65 subjects were enrolled and 46 completed the study. From the first to the third month after treatment, the symptom scores, FEV(1)% and PEF% improved significantly (t = 9.54, 13.17, 14.27, 12.4, 6.72, 6.59, 8.31, 5.22, and 5.96, respectively, all P < 0.01), and then maintained at relatively normal levels in a narrow range without significant progressive improvement during the later phases of the study. Meanwhile AHR declined abruptly in the first three months (t = 9.71, 12.04, and 14.31 in group A, B, C, respectively, all P < 0.01), followed by a slow but continuous improvement from the third to ninth month, and then maintained at a very low level. AHR disappeared in 4 cases but relapsed in 1 case after therapy withdrawal. The asthma clinical control level at the end point of group A, group B and group C were 93.3%, 53.3% and 93.8%, respectively (group A and group C versus group B, P < 0.01, respectively; group A versus group C, P > 0.05). There were fewer patients who underwent step-down therapy or withdrawal in group C compared to group B. However, patients in group C gained better asthma control and experienced less exacerbations compared to those in group B.. (1) Combined therapy with ICS plus LABA significantly improves symptoms, lung function and AHR of asthmatic patients. (2) Adjustment of therapy based only on clinical parameters may lead to early step-down or withdrawal and therefore asthma exacerbations. (3) PC(35) sGaw, an index of AHR, may be valuable in assessing asthma severity, evaluating the efficacy of treatment and guiding medication adjustment.

Topics: Adolescent; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Respiratory Function Tests; Salmeterol Xinafoate; Young Adult

To investigate the efficacy and mechanism of Fangchuan Mixture (FCM) in treating children with mild continuous asthma.. One hundred and seventy-five patients in the three groups were treated with FCM (A), Flixotide (B), and the combination of FCM and Flixotide (C), respectively for 12 weeks. Their condition of asthma and TCM syndrome were observed, peak expiratory flow (PEF) and serum levels of immunoglobulin (Ig), interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) were determined.. All the indexes determined were improved significantly in the three groups after treatment (P <0.05). Paired comparison among groups showed that the improvements in non-asthma time, time required beta-receptor activator, expectoration, complexion, appetite, and increasing serum IFN-gamma after treatment were superior in Group C than in Group A and B (P <0.05); the improvements in hidrosis, faint pulse and decreasing serum IL-4 level in Group A and C were better than those in Group B (P <0.05), and the effect for alleviating symptoms of rhinitis such as nasal obstruction and nasal discharge in Group C was more significant than that in Group B (P <0.05).. FCM could attenuate the allergic inflammation of bronchi to improve its hypersensitive state in children with asthma, and shows a cooperative action with Flixotide.

Topics: Adolescent; Androstadienes; Asthma; Bronchodilator Agents; Child; Child, Preschool; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Fluticasone; Humans; Male; Phytotherapy; Treatment Outcome

The aim of this study was to assess asthma control using salmeterol plus fluticasone propionate (FP) in combination (SFC) versus salmeterol or FP as monotherapy in patients with mild to moderate asthma.. In this randomised, double-blind, parallel-group study, 322 symptomatic patients were recruited, of which 282 were randomised to receive either salmeterol (50 microg), FP (250 microg), or SFC (50 microg/250 microg), via a single Diskus inhaler twice daily for 12 months. Outcome variables included the number of patients requiring an increase in study medication and the number experiencing 2 exacerbations during the 12-month treatment period. Airway hyper-responsiveness (AHR) and lung function tests were performed at clinic visits. Peak expiratory flow, rescue medication use, symptom scores and adverse events were recorded in diary cards.. Fewer patients required an increase in study medication with SFC (10.5%) than with either FP (34.8%) or salmeterol (61.1%) (P<0.001). Significantly fewer patients experienced 2 exacerbations with SFC (4.2%), compared with FP (17.4%; P<0.01) or salmeterol (40%; P<0.001). SFC improved AHR to a significantly greater extent than FP (methacholine PC20=1.8 mg/ml vs. 1.1 mg/ml; P<0.05) or salmeterol (methacholine PC20=1.8 mg/ml vs. 0.7 mg/ml; P<0.001).. The protection against exacerbations may be attributed to better control of inflammation, AHR and lung function parameters achieved with salmeterol and FP in combination, compared with either treatment alone.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Vital Capacity

In this economic evaluation, conducted alongside a randomized, double-blind clinical trial, economic data were collected from 339 patients with moderate-persistent asthma randomized to receive twice-daily, double-blind treatment with budesonide/formoterol 160/4.5 microg in a single inhaler (n=166) or fluticasone propionate 250 microg (n=173) for 12 weeks. The mean number of episode-free days (EFD) per patient was significantly greater in the budesonide/formoterol group than the fluticasone group (48.71 compared with 42.34, P=0.0185). Data on medication use, visits to healthcare professionals, and hospitalization were pooled across all six countries and combined with German and Dutch unit cost data to calculate total healthcare costs. Using German unit costs, budesonide/formoterol was associated with significantly lower total healthcare costs per patient over the 12-week period compared with fluticasone (euro 131 compared with euro 210, P=0.0043). Using Dutch unit costs, total healthcare costs were slightly numerically lower in the budesonide/formoterol group than the fluticasone group (euro 102 compared with euro 104), but the difference did not reach statistical significance. Budesonide/formoterol in a single inhaler is more effective than a higher microgram dose of fluticasone alone. It is cost-neutral and may provide cost-savings in some countries.

Topics: Adult; Aged; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Cost-Benefit Analysis; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Health Care Costs; Humans; Middle Aged

The aim of this study was to evaluate whether fluticasone propionate (FP) is effective as well as prednisone (P) in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbations not requiring hospitalization. We measured, in a parallel-group, double-blind double-dummy, randomized study, sputum and blood inflammatory cell counts and soluble mediators in 37 asthmatic subjects during a spontaneous exacerbation of asthma (Visit 1) and after a 2 week (Visit 2) treatment with inhaled FP (1000microg bid) (Group A, n=18) or a reducing course of oral P (Group B, n=19). Asthma exacerbation was accompanied by sputum eosinophilia (eosinophils >2%) in almost all patients (95%). FP improved FEV(1) (from 53.9%+/-16.8 at Visit 1 to 76.4%+/-21.2 at Visit 2, p=0.0001) and reduced the percentage of sputum eosinophils (from 38%[0-78] to 3%[1-31, p=0.0008) as well as oral P (FEV(1): from 51.5%+/-14.4 to 83.6%+/-21.1, p=0.0001; sputum eosinophils: from 52%[1-96] to 11%[0-64], p=0.0003). At Visit 2, sputum eosinophils were significantly lower in Group A than in Group B. P but not FP induced significant decrease in blood and sputum ECP. Oxygen saturation, PEF variability, symptom score and use of rescue medication similarly improved in both groups. We conclude that FP is effective at least as well as P in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbation. However, the cost/effectiveness ratio of this option should be further evaluated.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Androstadienes; Asthma; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophil Cationic Protein; Eosinophilia; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nausea; Oximetry; Prednisone; Recurrence; Severity of Illness Index; Sputum; Treatment Outcome

Inhaled corticosteroids are the mainstay of therapy in asthma, but local and systemic side effects and adherence remain a concern. Ciclesonide is an inhaled corticosteroid with on-site lung activation that provides potent anti-inflammatory activity and has been shown to have a good safety profile, even at high doses.. The aim of this study was to compare the efficacy and safety of once-daily ciclesonide versus twice-daily fluticasone propionate at comparable daily doses in patients with asthma.. In this multicenter, randomized, double-blind, double-dummy, parallel group study, 529 patients were randomized to ciclesonide 160 microg once daily or fluticasone propionate 88 microg twice daily for 12 weeks. The primary endpoint was change in lung function.. Both ciclesonide and fluticasone propionate significantly improved forced expiratory volume in 1s, forced vital capacity, and morning peak expiratory flow compared with baseline (p<0.0001 for all variables). Both medications reduced asthma symptoms and rescue medication use within the first 24 h. At the tested dose, both medications were equally safe and well tolerated.. Ciclesonide 160 microg once daily was as effective as fluticasone propionate 88 microg twice daily in improving lung function and asthma symptoms, and in reducing rescue medication use in patients with asthma.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Pregnenediones; Respiratory Function Tests; Vital Capacity

In order to assess whether the administration of salmeterol/fluticasone propionate combination (50/250 mcg by Diskus) for 1 week induces tolerance to the bronchoprotective effect of salmeterol on allergen challenge, a single-blind, cross-over study was carried out. We studied nine subjects (eight men and one woman; mean age+/-SD: 31.3+/-11.0 yr) with mild intermittent allergic asthma, never treated with regular beta2-agonists or inhaled corticosteroids. In a previous allergen challenge all subjects had shown a positive early airway response (EAR) to allergen. They underwent allergen challenge after 1-week treatment with placebo and a single dose of placebo immediately before allergen challenge (T1), or 1-week treatment with placebo and a single dose of salmeterol/fluticasone immediately before allergen challenge (T2), or 1-week treatment with salmeterol/fluticasone combination bid and a single dose of salmeterol/fluticasone immediately before allergen challenge (T3). EAR was evaluated both as maximum decrease in FEV1 (MaxDeltaFEV1 %) after allergen challenge and as area under FEV1 -time curve. MaxDeltaFEV1 % during allergen challenge protected by placebo (T1) was significantly greater than MaxDeltaFEV1 % during allergen challenges protected by single dose of salmeterol/fluticasone (T2) and by salmeterol/fluticasone 1-week treatment (T3). No difference was found in MaxDeltaFEV1 % between T2 and T3. The same results were observed also after computing the area under the curve for each challenge. When individually considered, all subjects were protected against EAR (protection index > or = 80%) at T2, while at 3 seven out of nine subjects were still protected against EAR. In conclusion, the simultaneous administration of salmeterol and fluticasone in the same device prevents in almost 80% of examined subjects the development of tolerance to the protective effect of salmeterol on allergen challenge. This observation may contribute to explain the positive interaction between inhaled beta2-agonists and corticosteroids in the long-term treatment of asthma.

Topics: Administration, Inhalation; Adult; Albuterol; Allergens; Androstadienes; Asthma; Bronchodilator Agents; Cross-Over Studies; Drug Tolerance; Female; Fluticasone; Humans; Male; Respiratory Function Tests; Salmeterol Xinafoate; Single-Blind Method

Outcome data are needed to base recommendations for controller asthma medication use in school-aged children.. We sought to determine intraindividual and interindividual response profiles and predictors of response to an inhaled corticosteroid (ICS) and a leukotriene receptor antagonist (LTRA).. An ICS, fluticasone propionate (100 mug twice daily), and an LTRA, montelukast (5-10 mg nightly, age dependent), were administered to children ages 6 to 17 years with mild-to-moderate persistent asthma using only as-needed bronchodilators in a multicenter, double-masked, 2-sequence, 16-week crossover trial. Clinical, pulmonary, and inflammatory responses to these controllers were evaluated.. Improvements in most clinical asthma control measures occurred with both controllers. However, clinical outcomes (asthma control days [ACDs], the validated Asthma Control Questionnaire, and albuterol use), pulmonary responses (FEV(1)/forced vital capacity, peak expiratory flow variability, morning peak expiratory flow, and measures of impedance), and inflammatory biomarkers (exhaled nitric oxide [eNO]) improved significantly more with fluticasone than with montelukast treatment. eNO was both a predictor of ACDs (P = .011) and a response indicator (P = .003) in discriminating the difference in ACD response between fluticasone and montelukast.. The more favorable clinical, pulmonary, and inflammatory responses to an ICS than to an LTRA provide pediatric-based group evidence to support ICSs as the preferred first-line therapy for mild-to-moderate persistent asthma in children. eNO, as a predictor of response, might help to identify individual children not receiving controller medication who achieve a greater improvement in ACDs with an ICS compared with an LTRA.

Topics: Acetates; Adolescent; Androstadienes; Asthma; Child; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Nitric Oxide; Quinolines; Sulfides

Inhaled corticosteroids (ICSs) delivered by metered-dose inhalers that contain chlorofluorocarbon propellants are being discontinued because of the harmful effects of chlorofluorocarbon on the ozone layer. Therefore, some metered-dose inhaler products are being reformulated with "ozone-friendly" hydrofluoroalkane propellants.. To evaluate treatment with fluticasone propionate hydrofluoroalkane inhalation aerosol, 88, 220, and 440 microg twice daily, vs placebo in patients with asthma receiving an ICS.. Randomized, double-blind, parallel-group, 12-week study.. Mean morning predose percent predicted forced expiratory volume in 1 second increased by 2.2%, 3.2%, and 4.6% in the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively, compared with an 8.3% decrease for placebo (P < .001 vs placebo for all groups). Secondary pulmonary function end points and asthma symptoms showed similar improvements compared with placebo. Discontinuation from the study due to lack of efficacy was 50% in the placebo group and 11%, 10%, and 6% in the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively. At week 12, the probability of remaining in the study was 0.89, 0.90, and 0.94 for the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively, vs 0.45 for the placebo group (P < .001 for all). Changes in 24-hour urinary cortisol excretion rates were similar among treatment groups.. Fluticasone propionate hydrofluoroalkane, previously shown to be a clinically suitable alternative to fluticasone propionate chlorofluorocarbon, was effective and well tolerated. The ability to switch from fluticasone propionate chlorofluorocarbon and other chlorofluorocarbon-containing ICSs to fluticasone propionate hydrofluoroalkane without sacrificing asthma control or tolerability will facilitate a smooth transition to this nonchlorofluorocarbon-containing medicinal.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Aged, 80 and over; Androstadienes; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate

Ciclesonide is a novel, lung-activated, inhaled corticosteroid with once-daily efficacy and potent anti-inflammatory activity. The aim of the study was to compare the effect of ciclesonide and fluticasone propionate on exhaled nitric oxide (FENO), pulmonary function, and other parameters used in clinical evaluation of patients with mild allergic asthma. The study indicates that ciclesonide (in a daily dose of either 80 or 160 microg) induces both a faster and stronger decrease of FENO in comparison with fluticasone (100 microg twice daily). In both groups of patients treated with ciclesonide, the highest decrease in FENO levels was observed after 2 weeks of treatment. In the group of patients treated with fluticasone, this maximum effect was not observed till 8 weeks. An improvement in spirometric indices was observed in all groups studied. Statistical differences between the groups were not found; however, there was a trend toward higher increase in the group receiving 160 microg of ciclesonide. In all groups studied we observed clinical improvement (asthmatic symptoms and consumption of rescue medication were reduced), but there were no significant differences between these groups. Our results indicate that ciclesonide, compared with fluticasone, has stronger anti-inflammatory activity in patients with mild allergic asthma.

Topics: Adult; Androstadienes; Anti-Allergic Agents; Asthma; Breath Tests; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nitric Oxide; Pregnenediones; Treatment Outcome

Addition of the long acting beta2 agonist salmeterol to inhaled corticosteroids leads to better symptomatic asthma control than increasing the dose of inhaled corticosteroids. However, little is known about the long term effects of adding salmeterol on the asthmatic inflammatory process, control of which is considered important for the long term outcome of asthma.. After a 4 week fluticasone run-in period, 54 patients with allergic asthma were randomised to receive twice daily treatment with fluticasone 250 microg with or without salmeterol 50 microg for 1 year in a double blind, parallel group design (total daily dose of fluticasone 500 microg in both treatment groups). Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein concentrations. Secondary outcomes were neutrophil associated sputum parameters and a respiratory membrane permeability marker. The effects on allergen induced changes were determined before and at the end of the treatment period.. Adding salmeterol to fluticasone resulted in improved peak expiratory flow, symptom scores, rescue medication usage, and bronchial hyperresponsiveness (p < 0.05 for all). There was no sustained effect on sputum cell differential counts and cytokine concentrations during the treatment period or on changes induced by allergen challenge at the end of treatment (p > 0.05). However, adding salmeterol significantly reduced sputum ratios of alpha2-macroglobulin and albumin during the treatment period (p = 0.001).. The addition of salmeterol to fluticasone produces no sustained effect on allergen induced cellular bronchial inflammation but leads to a significant improvement in size selectivity of plasma protein permeation across the respiratory membrane. This may contribute to the improved clinical outcome seen in patients with allergic asthma when a long acting beta2 agonist is combined with inhaled corticosteroids.

Topics: Administration, Inhalation; Adult; Albuterol; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchitis; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Fluticasone; Humans; Male; Middle Aged; Salmeterol Xinafoate; Treatment Outcome

This study compared the efficacy and tolerability of the combination of fluticasone propionate (FP) and salmeterol (SAL) delivered via a single hydrofluoroalkane (HFA) 134a metered-dose inhaler (MDI) with those of its 2 components alone delivered via a chlorofluorocarbon (CFC) MDI and placebo (PLA) delivered via HFA MDI in adolescent and adult patients with persistent asthma that was not controlled by medium doses (equivalent to FP 440-660 microg/d) of inhaled corticosteroids (ICSs).. This was a randomized, double-blind,placebo-controlled, parallel-group study consisting of a 2-week, single-blind, placebo run-in period followed by a 12-week, double-blind treatment period. Participants had to be > or =12 years of age and have a diagnosis of asthma requiring pharmacotherapy for at least 6 months before the study. Patients had to have used ICS therapy for > or =3 months before the study and at a consistent dose for the previous month. Lack of asthma control was defined as a forced expiratory volume in 1 second (FEV(1)) that was 40% to 85% of the predicted value. Patients could not enter the double-blind treatment period if they had 3 days when they required >12 puffs of rescue albuterol per day or >3 nighttime awakenings due to asthma that required treatment with albuterol during the 7 days before the randomization visit. Patients were randomized to receive one of the following treatments delivered via MDI twice daily for 12 weeks: FSC 220/42 microg HFA (2 inhalations of FSC 110/21 microg; 125 microg/21 microg ex-valve); FP 220 microg CFC (2 inhalations of FP 110 microg); SAL 42 microg CFC (2 inhalations of 21 microg); or 2 inhalations of PLA HFA. The primary efficacy end point for FSC versus FP was the mean area under the 12-hour serial FEV(1) curve relative to the prerandomization baseline (FEV(1) AUC(bl)). The primary efficacy end points for FSC versus SAL were the mean change from baseline in morning predose FEV(1) at end point and the probability of not being withdrawn from the study due to worsening asthma. Tolerability assessments included electrocardiograms, routine clinical laboratory tests, vital signs, oropharyngeal examinations, and physical examinations. Adverse events were assessed at each clinic visit.. Thirty-two adolescent and 333 adult patients were randomly assigned to receive double-blind treatment. The treatment groups were comparable at baseline with respect to demographic characteristics (mean age, 38-41 years; white race, 78%-88%) and pulmonary function (mean percent predicted FEV(1), 68%-69%; mean asthma symptom score, 1.6 [scale 0-5]; and mean daily albuterol use, 3.1 puffs). After 12 weeks of treatment, the mean FEV(1) AUC(bl) was significantly greater in patients who received FSC compared with those who received FP, SAL, or PLA (7.0, 3.6, 5.3, and 1.4 L-h, respectively; all comparisons, P < or = 0.020). At end point, the mean change from baseline in morning predose FEV(1) for FSC was significantly greater than that for FP, SAL, and PLA (0.41, 0.19, 0.15, and -0.12 L; all comparisons, P < or = 0.001). During 12 weeks of treatment, 7% of patients receiving FSC were withdrawn due to worsening asthma, compared with 24% of patients receiving SAL and 54% of patients receiving PLA (P < 0.001); 11% of patients receiving FP were withdrawn due to worsening asthma. Treatment with FSC resulted in significant improvements in morning and evening peak expiratory flow compared with FP, SAL, and PLA (both, P < 0.001); need for rescue albuterol compared with FP and PLA (P < or =0.005); and asthma symptom scores compared with PLA (P < 0.001). The tolerability of FSC was similar to that of FP or SAL alone. The incidence of possibly drug-related adverse events was generally similar across treatment groups, and the most common (occurring in > or= 2% of patients) were headache (1%-4%), throat irritation (1%-2%), candidiasis of the mouth/throat (0%-2%), unspecified oropharyngeal plaques (0%-2%), and palpitations (0%-2%).. In these adolescent and adult patients whose asthma was not controlled by medium doses of an ICS, FSC delivered via HFA 134a MDI (2 inhalations of 110/21-microg strength administered BID) was more effective in improving lung function than FP or SAL monotherapy or PLA. All treatments were well tolerated.

Topics: Adolescent; Adult; Aerosol Propellants; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Follow-Up Studies; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Middle Aged; Salmeterol Xinafoate; Spirometry; Time Factors; Treatment Outcome

Allergic rhinitis (AR) precedes and is often associated with bronchial asthma. Indeed, local and systemic inflammations in both conditions are very similar. Cysteinyl-leukotrienes (cys-LTs) are generated during early- and late-phase allergic reactions and induce smooth-muscle contraction, microvascular leakage, and mucous hypersecretion. Cys-LTs are detected in exhaled breath condensate (EBC) of asthmatics and regardless of bronchial symptoms, they are also found in EBC of rhinitic patients.. To evaluate cys-LTs in EBC of allergic patients and to assess the activity of nasal fluticasone propionate (FP) on EBC cys-LTs levels.. Cys-LTs coefficient of variation (CV) was evaluated from different EBC in 5 healthy volunteers. Cys-LTs levels from EBCs in 13 healthy controls and 56 allergic rhinitic (n=31) and rhinitic/asthmatic (n=25) patients were also evaluated at baseline. Subsequently patients were randomized to receive either FP 100 microg/day per nostril or placebo for 2 weeks and then re-evaluated for EBC cys-LTs.. The CV was 14.12%. EBC cys-LTs in allergic patients were significantly higher than in healthy subjects (70.9 vs. 20.6 pg/mL (median), P<0.05), while it did not differ between asthmatic/rhinitic and purely rhinitic patients. Treatment significantly reduced cys-LTs (from 93.6 to 19.9 pg/mL, P<0.001). This effect was evident both in asthmatic/rhinitic and in rhinitic patients.. Treatment of AR with FP significantly reduces the levels of cys-LTs, major noninvasive markers of lower airway inflammation, suggesting that upper and lower airway inflammation is present and should be thus treated as a whole in subjects with AR with and without asthma.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Biomarkers; Breath Tests; Bronchi; Cysteine; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Leukotrienes; Male; Rhinitis, Allergic, Seasonal; Vital Capacity

Lung inflammation and injury is critical in cystic fibrosis. An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence.. To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations.. Multicenter randomized double-blind placebo-controlled trial in 18 pediatric and adult UK centers. Eligibility criteria included age>6.0 yr, FEV1>or=40% predicted, and corticosteroid use>3 mo. During the 2-mo run-in period, all patients received fluticasone; they then took either fluticasone or placebo for 6 mo.. Fluticasone group: n=84, median age 14.6 yr, mean (SD) FEV1 76% (18); placebo group: n=87, median age 15.8 yr, mean (SD) FEV1 76% (18). There was no difference in time to first exacerbation (primary outcome) with hazard ratio (95% confidence interval) of 1.07 (0.68 to 1.70) for fluticasone versus placebo. There was no effect of age, atopy, corticosteroid dose, FEV1, or Pseudomonas aeruginosa status. There was no change in lung function or differences in antibiotic or rescue bronchodilator use. Fewer patients in the fluticasone group withdrew from the study due to lung-related adverse events (9 vs. 15%); with a relative risk (95% confidence interval) of 0.59 (0.23-1.48) fluticasone versus placebo.. In this study population (applicable to 40% of patients with cystic fibrosis in the UK), it appears safe to consider stopping inhaled corticosteroids. Potential advantages will be to reduce the drug burden on patients, reduce adverse effects, and make financial savings.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Age Factors; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Cystic Fibrosis; Double-Blind Method; Feasibility Studies; Female; Fluticasone; Follow-Up Studies; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Placebos; Pseudomonas aeruginosa; Safety; Withholding Treatment

The Gaining Optimal Asthma ControL (GOAL) study has shown the superiority of a combination of salmeterol/fluticasone propionate (SFC) compared with fluticasone propionate alone (FP) in terms of improving guideline defined asthma control.. Clinical and economic data were taken from the GOAL study, supplemented with data on health related quality of life, in order to estimate the cost per quality adjusted life year (QALY) results for each of three strata (previously corticosteroid-free, low- and moderate-dose corticosteroid users). A series of statistical models of trial outcomes was used to construct cost effectiveness estimates across the strata of the multinational GOAL study including adjustment to the UK experience. Uncertainty was handled using the non-parametric bootstrap. Cost-effectiveness was compared with other treatments for chronic conditions.. Salmeterol/fluticasone propionate improved the proportion of patients achieving totally and well-controlled weeks resulting in a similar QALY gain across the three strata of GOAL. Additional costs of treatment were greatest in stratum 1 and least in stratum 3, with some of the costs offset by reduced health care resource use. Cost-effectiveness by stratum was 7600 pound (95% CI: 4800-10,700 pound) per QALY gained for stratum 3; 11,000 pound (8600-14,600 pound) per QALY gained for stratum 2; and 13,700 pound (11,000-18,300 pound) per QALY gained for stratum 1.. The GOAL study previously demonstrated the improvement in total control associated with the use of SFC compared with FP alone. This study suggests that this improvement in control is associated with cost-per-QALY figures that compare favourably with other uses of scarce health care resources.

Topics: Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Cost-Benefit Analysis; Double-Blind Method; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Models, Statistical; Outcome Assessment, Health Care; Quality of Life; Quality-Adjusted Life Years; Time Factors; Treatment Outcome; United Kingdom

Newer generations and formulations of inhaled corticosteroids have necessitated the development of a clinically relevant model to compare their clinical potency.. We evaluated whether sputum eosinophil counts could demonstrate a dose-response to inhaled corticosteroids, and compared the response with other inflammatory markers.. Fourteen steroid-naive patients with asthma with an initial sputum eosinophilia of > or = 2.5% entered a 6-week sequential, placebo-controlled, patient-blinded, cumulative dose-response study. After 7 days of placebo, they received incremental doses of fluticasone propionate (FP), 50, 100, 200, and 400 microg/d, each for 7 days. Measurements were made of sputum and blood eosinophils, exhaled nitric oxide, spirometry, airway responsiveness to methacholine (methacholine PC20), and symptom scores before and after each dose.. Sputum eosinophils and exhaled nitric oxide were extremely sensitive to the effects of FP, and exhibited significant dose-dependent reductions of 99.4% and 99.8 parts per billion, respectively, where each variable was expressed per 100 microg/d FP. This compared with a 0.5 doubling dose increase of airway responsiveness to methacholine and a 0.3 decrease in symptom scores. Airway responsiveness to methacholine was the only variable that increased throughout the study.. These results suggest that the model of eosinophilic bronchitis could be used to compare the effect of cumulative doses of an inhaled corticosteroid delivered by different types of delivery systems or preparations using a relatively small number of patients.. Future clinical studies based on this model will allow clinicians to make informed decisions regarding the relative potencies of different inhaled corticosteroids.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Biomarkers; Bronchitis; Dose-Response Relationship, Drug; Eosinophil Cationic Protein; Eosinophilia; Fibrinogen; Fluticasone; Humans; Nitric Oxide; Serine Endopeptidases; Single-Blind Method; Sputum; Tryptases

It is unknown whether inhaled corticosteroids can modify the subsequent development of asthma in preschool children at high risk for asthma.. We randomly assigned 285 participants two or three years of age with a positive asthma predictive index to treatment with fluticasone propionate (at a dose of 88 mug twice daily) or masked placebo for two years, followed by a one-year period without study medication. The primary outcome was the proportion of episode-free days during the observation year.. During the observation year, no significant differences were seen between the two groups in the proportion of episode-free days, the number of exacerbations, or lung function. During the treatment period, as compared with placebo use, use of the inhaled corticosteroid was associated with a greater proportion of episode-free days (P=0.006) and a lower rate of exacerbations (P<0.001) and of supplementary use of controller medication (P<0.001). In the inhaled-corticosteroid group, as compared with the placebo group, the mean increase in height was 1.1 cm less at 24 months (P<0.001), but by the end of the trial, the height increase was 0.7 cm less (P=0.008). During treatment, the inhaled corticosteroid reduced symptoms and exacerbations but slowed growth, albeit temporarily and not progressively.. In preschool children at high risk for asthma, two years of inhaled-corticosteroid therapy did not change the development of asthma symptoms or lung function during a third, treatment-free year. These findings do not provide support for a subsequent disease-modifying effect of inhaled corticosteroids after the treatment is discontinued. (ClinicalTrials.gov number, NCT00272441.).

Topics: Administration, Inhalation; Analysis of Variance; Androstadienes; Asthma; Bronchodilator Agents; Child, Preschool; Disease Progression; Disease-Free Survival; Female; Fluticasone; Growth; Humans; Male; Regression Analysis; Respiratory Physiological Phenomena; Respiratory Sounds; Risk Factors; Treatment Outcome

The present study evaluated the steroid-sparing effect of subcutaneous SQ-standardized specific immunotherapy (SIT) in moderate and severe house dust mite (HDM) allergic asthmatics.. Fifty-four adult asthmatics allergic to HDM requiring at least inhaled corticosteroids (ICS) doses equivalent to 500 microg fluticasone propionate daily were randomized to subcutaneous SIT or placebo injections for a period of 3 years. The minimum required ICS dose, 4 week diary of asthma symptom score, use of rescue medication, peak expiratory flow (PEF) measurements and visual analog scale for asthma symptoms were assessed before start of treatment and after 1, 2 and 3 years of treatment.. In patients with moderate and severe asthma, the reduction in ICS was statistical significant after 2 years of treatment (P = 0.03) but not after 3 years. The median reductions were 82% and 42% after the third year for active and placebo respectively. In patients with moderate persistent asthma the reduction was statistical significant larger for those treated with SIT compared with placebo after year 2 and year 3. The median reductions after 3 years were 90% for SIT and 42% for placebo (P = 0.04). Despite significant steroid reduction, there was no difference in asthma assessments between the two groups. No serious reactions related to SIT injections were seen.. This study shows that SIT with a SQ-standardized HDM extract is safe. An ICS sparing effect was evident in patients with moderate persistent asthma.

Topics: Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Antigens, Dermatophagoides; Asthma; Bronchodilator Agents; Desensitization, Immunologic; Double-Blind Method; Female; Fluticasone; Humans; Male; Nebulizers and Vaporizers

Current asthma guidelines recommend inhaled glucocorticoids administered via pressurized metered-dose inhaler (MDI) with a holding chamber as the preferred therapy for young children with asthma.. To evaluate the efficacy and safety of fluticasone propionate chlorofluorocarbon MDI use in preschool-aged children with asthma.. Randomized, double-blind, placebo-controlled, parallel-group study of 332 children aged 24 to 47 months with asthma. Fluticasone propionate chlorofluorocarbon, 44 or 88 microg twice daily, or placebo (chlorofluorocarbon propellant alone) administered for 12 weeks via MDI with a valved holding chamber and an attached face mask. The primary efficacy measure was average change in 24-hour daily asthma symptom scores. Safety assessments included adverse events, 12-hour urinary cortisol excretion, and growth.. Treatment failure (ie, asthma exacerbation) occurred in approximately half as many fluticasone propionate-treated patients (13%-14%) as placebo-treated patients (24%). Compared with placebo users, patients treated with fluticasone propionate, 88 microg twice daily, had a 13% greater improvement in the mean proportion of symptom- and albuterol-free days (P = .02); asthma symptom scores and albuterol use were also significantly reduced. Patients treated with fluticasone propionate, 44 microg twice daily, had greater improvements than placebo-treated patients; however, differences did not reach statistical significance. At end point, the growth velocities of fluticasone propionate-treated patients were within the range of those of placebo-treated patients. No clinically relevant changes in 12-hour overnight urinary cortisol excretion were observed.. Compared with placebo use, fluticasone propionate, 88 microg administered twice daily, significantly reduced asthma exacerbations, asthma symptoms, and rescue albuterol use and was well tolerated, with no clinically relevant systemic effects, as measured by growth velocity or 12-hour urinary cortisol excretion levels.

Topics: Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Body Height; Bronchodilator Agents; Child, Preschool; Double-Blind Method; Female; Fluticasone; Humans; Male; Metered Dose Inhalers; Peak Expiratory Flow Rate

Inhaled corticosteroids (ICSs) have been shown to reverse epithelial damage and decrease lamina reticularis thickness in patients with asthma.. This study investigated whether clinical asthma control and airway inflammation could be maintained after switching therapy from medium-dose fluticasone propionate (FP) to low-dose FP administered with the long-acting beta2-agonist (LABA) salmeterol.. Eighty-eight subjects (age, > or =18 years) who, during open-label screening, demonstrated improved asthma control after an increase from 100 microg of FP twice daily to 250 microg of FP twice daily were randomized to receive 100/50 microg of FP/salmeterol through a Diskus inhaler (GlaxoSmithKline, Research Triangle Park, NC) twice daily or continue 250 microg of FP twice daily through a Diskus inhaler for 24 weeks. Clinical outcomes were monitored, and bronchial biopsy specimens and bronchoalveolar lavage fluid were obtained before and after 24 weeks of treatment.. There were no significant differences between treatments with respect to eosinophils in the bronchial mucosa and bronchoalveolar lavage fluid; mucosal mast cells, neutrophils, or CD3+, CD4+, CD8+, or CD25+ T lymphocytes; or concentration of mediators (GM-CSF, IL-8, and eosinophil cationic protein). The 2 treatments were not different with respect to lamina reticularis thickness. Consistent with the airway inflammatory measures, clinical and physiologic measures of asthma control were also similar.. This study demonstrates that control of asthma and airway inflammation is maintained over the 24-week treatment period when patients requiring a medium-dose ICS are switched to a lower-dose ICS with a LABA.. A lower-dose ICS with a LABA is effective in controlling inflammation and providing clinical asthma control, confirming current guideline recommendations.

Topics: Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Bronchoalveolar Lavage Fluid; Female; Fluticasone; Humans; Immunohistochemistry; Male; Middle Aged; Prospective Studies; Salmeterol Xinafoate

Inhaled corticosteroids are highly effective in asthma, reducing inflammatory markers and bronchial hyperresponsiveness. Cysteinyl-leukotrienes are major mediators of airway obstruction and display proinflammatory effects. Although the synthesis of leukotrienes is not affected by corticosteroid treatment, the influence of corticosteroids on the leukotriene pathway remains unresolved.. We investigated whether or not bronchial responsiveness to leukotriene (LT) D(4) is reduced by fluticasone propionate in subjects with asthma.. In 13 subjects with mild asthma, inhalation challenges with methacholine and LTD(4) were performed on consecutive days before and after 2 weeks of treatment with inhaled fluticasone 500 mug, twice daily, in a double-blind, randomized, placebo-controlled study with crossover design and 3 weeks of washout between periods. Exhaled nitric oxide was measured as a marker of corticosteroid responsiveness, and baseline urinary LTE(4) concentrations as an index of cysteinyl-leukotriene biosynthesis.. Fluticasone produced a significant decrease in methacholine responsiveness, corresponding to 2.6-fold shift in the PD(20) FEV(1), and a significant reduction in the levels of exhaled nitric oxide. By contrast, bronchial responsiveness to LTD(4) in the same subjects was unaffected by fluticasone, as were urinary LTE(4) concentrations.. These new data indicate that neither the biosynthesis nor the actions of leukotrienes appear to be sensitive to inhaled corticosteroids.. The study provides mechanistic support for the additive therapeutic efficacy of antileukotrienes and inhaled corticosteroids in asthma.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Bronchi; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Leukotriene D4; Leukotriene E4; Male; Methacholine Chloride

Ciclesonide (CIC) is an inhaled corticosteroid (ICS) with high anti-inflammatory activity and low incidence of local and systemic adverse effects. The objective of this study was to compare the efficacy and safety of CIC with fluticasone propionate (FP) in children and adolescents with persistent asthma. This was a 12-week, randomized, double blind, parallel-group study. After a 2-to 4-week baseline period, a total of 556 children (ages 6-15 years) with asthma (forced expiratory volume in 1 sec [FEV(1)], 50% to 90% predicted) were treated twice daily with CIC 80 microg (ex-actuator, equivalent to 100 microg ex-valve) or FP 88 microg (ex-actuator, equivalent to 100 microg ex-valve) administered via a hydrofluoroalkane-propelled metered-dose inhaler. A statistically significant increase from baseline was observed in FEV(1) for both CIC (285 +/- 16 ml) and FP (285 +/- 15 ml) (P < 0.0001 for both) and in morning and evening peak expiratory flow (P < 0.0001 for both). Significant improvements were seen in asthma symptoms, use of rescue medication, and asthma symptom-free days in both treatment groups, without any differences between the treatment groups in changes from baseline. Two FP-treated patients experienced oral candidiasis and one patient experienced voice alteration. Creatinine-adjusted 24-hr urine cortisol levels increased from baseline levels by 10% in the CIC group (P < 0.05) and by 6% in the FP group (not significant). The efficacy and safety of CIC 160 microg/day were comparable to those of FP 176 microg/day in children with asthma.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Pregnenediones; Respiratory Function Tests

Inhaled corticosteroids are not as effective as oral corticosteroids in school-aged children with severe acute asthma. It is uncertain how inhaled corticosteroids compare with oral corticosteroids in mild to moderate exacerbations.. The purpose of this work was to determine whether there is a significant difference in the percentage of predicted forced expiratory volume in 1 second in children with mild to moderate acute asthma treated with either inhaled fluticasone or oral prednisolone.. This was a randomized, double-blind controlled trial conducted between 2001 and 2004 in a tertiary care pediatric emergency department. We studied a convenience sample of 69 previously healthy children 5 to 17 years of age with acute asthma and forced expiratory volume in 1 second at 50% to 79% predicted value; 41 families refused participation. Albuterol was given in the emergency department and salmeterol was given after discharge to all patients, as well as either 2 mg of fluticasone via metered dose inhaler and valved holding chamber in the emergency department plus 500 microg twice daily via Diskus for 10 doses after discharge (fluticasone group, N = 35) or 2 mg/kg of oral prednisolone in the emergency department plus 5 daily doses of 1 mg/kg of prednisolone after discharge (prednisolone group, N = 34). We measured a priori defined absolute change in percent predicted forced expiratory volume in 1 second from baseline to 4 and 48 hours in the 2 groups. RESULTS. At 240 minutes, the forced expiratory volume in 1 second increased by 19.1% +/- 12.7% in the fluticasone group and 29.8% +/- 15.5% in the prednisolone group. At 48 hours, this difference was no longer significant (estimated difference: 4.0 +/- 3.4; P = .14). The relapse rates by 48 hours were 12.5% and 0% in the fluticasone group and prednisolone group, respectively.. Airway obstruction in children with mild to moderate acute asthma in the emergency department improves faster on oral than inhaled corticosteroids.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Airway Obstruction; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Prednisolone; Treatment Outcome

This study was performed to determine the clinical characteristics of asthmatics with bronchial hyperresponsiveness (BHR) that could not be normalized by 6 months of treatment with a moderate dose of an inhaled corticosteroid (ICS).. Thirty-four symptomatic patients with mild to moderate asthma, who had never received any ICS, were treated with 200 mug of inhaled fluticasone propionate twice a day for 6 months. Spirometry, BHR to methacholine, exhaled nitric oxide (NO) and eosinophils in induced sputum were examined before and 2 and 6 months after beginning treatment.. FEV1 was increased and bronchial responsiveness, exhaled NO and sputum eosinophilia were significantly decreased 2 and 6 months after starting ICS treatment. Bronchial responsiveness was further decreased at 6 months together with a further increase in FEV1. In 13 patients, BHR was not normalized despite the 6 months of treatment. This group showed a higher prevalence of males, those with a smoking history and airflow limitation, a higher eosinophil count in the sputum following 6 months of treatment and a longer history of asthma. Multiple, stepwise, linear regression analysis showed that sputum eosinophilia and lower FEV1/FVC following 6 months of treatment and a longer history of asthma were significant independent determinants for BHR after 6 months of ICS treatment.. These findings suggest that the resistance to a moderate dose of ICS for BHR in asthmatics may be significantly associated with remained airflow limitation, eosinophilic airway inflammation resistive to moderate dose of ICS, and delayed introduction of ICS therapy.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Asthma; Bronchial Hyperreactivity; Bronchoconstriction; Bronchoconstrictor Agents; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Humans; Inflammation; Male; Methacholine Chloride; Middle Aged; Nitric Oxide; Respiratory Function Tests

To investigate the duration of bronchodilator action of a salmeterol/fluticasone combination (SFC) inhaler when administered in the evening to children with asthma.. A double-blind, placebo-controlled, cross-over study.. Hospital inpatient.. Fourteen children aged between 4 and 11 years with mild to moderate asthma (FEV(1) > 60% predicted) who exhibited a 15% increase in FEV(1) with bronchodilator.. SUBJECTS inhaled, in random order, either SFC (100/50 microg) or placebo, via accuhaler, at 20.00 hours on two separate occasions with at least 3 days between study days.. Lung function measurements including FEV(1), PEF, specific airways conductance (sGaw) and maximum expiratory flow at 25-75% of vital capacity were measured at baseline, 2, 12, 16, 20 and 24 h.. For all lung function parameters SFC resulted in significantly greater bronchodilation than placebo for at least 20 h after inhalation. At 24 h, the increase in FEV(1) and PEF compared with placebo was 0.08 L (95% confidence interval: -0.18 to 0.02, P = 0.16) and 27 L/min (95% confidence interval: -47 to -6, P = 0.004), respectively.. The single administration of SFC via an accuhaler in the evening resulted in significant bronchodilation for at least 20 h in children with asthma.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Male; Pulmonary Ventilation; Salmeterol Xinafoate

Combination of inhaled corticosteroids (ICS) with long acting beta2 agonists has been used increasingly in the treatment of moderate-severe asthma, however there is indefinitive data about their effect on bone loss. The aim of this study was to compare the effects of treatment with single ICS and combination of ICS with long acting beta2 agonists (combination therapy) on BMD and biomarkers of bone metabolism in adult patients with asthma over 1 year period. Forty-three patients with asthma were enrolled. Patients were separated into two groups according to their use of asthma drugs: single ICS or combination therapy (ICS plus long-acting inhaled beta2-agonist). Change in bone mineral density (BMD) and biochemical markers of bone metabolism were measured at baseline and at the end of 1 year. Mean ages and basal BMD of patients did not differ between the two groups (P > 0.05). The decrease in BMD was higher in the single ICS group than the combination therapy group, however there was no significant difference between them (P > 0.05). One year change (%) in BMD and biochemical markers of bone metabolism were not different between two groups (P > 0.05). In conclusion, use of ICS-in the range of doses used- does not seem to have an effect on the change of BMD. However, our data indicate a nonsignificant trend towards reducing bone loss with the use of combination therapy. Future studies are needed to provide definitive evidence for this trend to allow us suggesting combination therapy for minimizing bone loss.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Beclomethasone; Bone Density; Bone Resorption; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Osteoporosis; Salmeterol Xinafoate

Wheezing and asthma often begins in early childhood, but it is difficult to predict whether or not a wheezy infant will develop asthma. Some researchers suggest that treatment with inhaled corticosteroids at the first signs of wheezing in childhood could prevent the development of asthma later in life. However, other investigators have reported that although such treatment could help control symptoms, the benefits can disappear within months of stopping treatment. We tested our hypothesis that to prevent loss of lung function and worsening asthma later in childhood, anti-inflammatory treatment needs to be started early in life.. We did a randomised, double-blind, controlled study of inhaled fluticasone propionate 100 mug twice daily in young children who were followed prospectively and randomised after either one prolonged (>1 month) or two medically confirmed wheezy episodes. The dose of study drug was reduced every 3 months to the minimum needed. If the symptoms were not under control by 3 months, open-label fluticasone propionate 100 mug twice daily was added to the treatment. Children were followed-up to 5 years of age, at which point we gave their parents or guardians questionnaires, and measured the children's lung function (specific airways resistance [sR(aw)], forced expiratory volume in 1s [FEV1]) and airway reactivity (eucapnic voluntary hyperventilation [EVH] challenge). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN86717853.. We followed 1073 children prospectively, of whom 333 were eligible, and 200 of these began treatment (130 male, median age 1.2 years [range 0.5-4.9]; 101 placebo, 99 treatment); 173 (85 treatment, 88 placebo) completed the follow-up at age five years. The groups did not differ significantly in the proportion of children with current wheeze, physician-diagnosed asthma or use of asthma medication, lung function, or airway reactivity (percentage change in FEV1, adjusted mean for placebo 5.5% [95% CI -2.5 to 13.4]) vs for treatment 5.0% [-2.2 to 12.2], p=0.87). There were no differences in the results after adjustment for open-label fluticasone propionate, nor between the two groups in the time before the open-label drug was added (estimated hazard ratio 1.12 [95% CI 0.73-1.73], p=0.60), or the proportion needing the open-label drug (43 [42.57%] placebo, 41 [41.41%] treatment).. The early use of inhaled fluticasone propionate for wheezing in preschool children had no effect on the natural history of asthma or wheeze later in childhood, and did not prevent lung function decline or reduce airway reactivity.

Topics: Administration, Inhalation; Androstadienes; Asthma; Bronchodilator Agents; Child, Preschool; Double-Blind Method; Female; Fluticasone; Follow-Up Studies; Humans; Infant; Lung Volume Measurements; Male; Respiratory Sounds

In this randomized crossover study, 22 adult patients with moderate-to-severe persistent bronchial asthma were assigned to one of two groups. Patients in group 1 were administered fluticasone dry powder inhaler (DPI) for 8 weeks followed by a 2-week washout period, then hydrofluoroalkane-beclometasone dipropionate (HFA-BDP) for 8 weeks. After a further 2-week washout, they were again administered fluticasone DPI for 8 weeks. Patients in group 2 were assigned HFA-BDP followed by fluticasone PII and finally HFA-BDP over the same time periods. In both groups, no significant difference was observed in use of beta2-agonists and symptom score between the treatment periods; however, markers of pulmonary function were significantly higher when on HFA-BDP versus fluticasone DPI. Significant increases of morning peak expiratory flow (PEF) (p < 0.01), forced expiratory volume in 1 second (FEV1.0) (p < 0.01), V50 (p < 0.05), and V25 (p < 0.01) were observed at 18 weeks in group 1, whereas there were significant decreases of V50 (p < 0.05) at 18 weeks in group 2. No significant difference was noted in circulating eosinophil count and serum ECP between the 2 treatments; however, ECP in induced sputum and nitric oxide in expired gas were significantly lower (p < 0.05 and < 0.01, respectively) when on HFA-BDP versus fluticasone DPI. HFA-BDP might be delivered to small airways more effectively than fluticasone DPI.

Topics: Adrenergic beta-Agonists; Adult; Aerosol Propellants; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Cross-Over Studies; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Male; Medical Records; Metered Dose Inhalers; Middle Aged; Particle Size; Peak Expiratory Flow Rate

Currently, patients have to keep track of doses to determine when to replace their metered-dose inhalers (MDIs). This study evaluated the performance and patient satisfaction of a novel MDI with an integrated dose counter. In an open-label study at 38 outpatient centres, patients > or =12 years old with asthma or chronic obstructive pulmonary disease (COPD) received two actuations of fluticasone propionate/salmeterol 125/25 microg (115/21 microg ex-actuator) hydrofluoroalkane (ADVAIR) HFA) via MDI with counter twice a day until all 120 actuations were completed. Concordance between counter and diary recordings in patients who reported use of > or =90% of labelled actuations (completer population, n = 228) was high (discrepancy rate of 0.94%) and the incidence of device firing without changes in counter readings was low (0.13%). Mean expected actuations based on canister weights (114) were slightly lower than mean counter (121) and diary reported actuations (120). Upon study completion, 95% of patients were satisfied with the dose counter and 92% agreed it would help prevent them from running out of medication. Safety assessments (intent-to-treat population, n = 237) indicated that the drug was well tolerated. This integrated MDI counter may help patients maintain better disease control by enabling them to accurately track their medication supply.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Middle Aged; Patient Satisfaction; Powders; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Treatment Outcome

Recent studies suggest that there might be an association between albuterol use and worsening asthma in patients homozygous for arginine (Arg/Arg) at codon 16 of the beta-receptor. However, it is not known whether similar responses occur in Arg/Arg patients receiving long-acting beta2-agonists.. We sought to evaluate the effects of variation in the beta2-adrenergic receptor gene (ADRB2) on clinical response to salmeterol administered with fluticasone propionate.. Subjects (n = 183) currently receiving short-acting beta2-agonists were randomized to twice-daily therapy with salmeterol, 50 microg, administered with fluticasone propionate, 100 microg, in a single inhaler or daily therapy with montelukast for 12 weeks, followed by a 2- to 4-day run-out period.. There was sustained and significant improvement (P < .001) over baseline in all measures of asthma control in subjects receiving salmeterol, regardless of Arg16Gly genotype. Morning peak expiratory flow in subjects with the Arg/Arg genotype showed 89.0 +/- 16.1 L/min improvement over baseline compared with 93.7 +/- 12.7 L/min for Gly/Gly subjects and 92.5 +/- 11.9 L/min for Arg/Gly subjects. Pairwise changes were similar for Arg/Arg compared with Gly/Gly or Arg/Gly genotypes (estimated differences, 4.7 L/min and 3.5 L/min, respectively). Responses did not appear to be modified by haplotype pairs. During the run-out period, all subjects had predictable and similar decreases in measures of asthma control, with no differences between genotypes.. Response to salmeterol does not vary between ADRB2 genotypes after chronic dosing with an inhaled corticosteroid.. Analyses from this study indicate that genetic polymorphisms leading to Arg16Gly sequence changes within the beta2-adrenergic receptor do not affect patients' responses to recommended asthma therapy with salmeterol and fluticasone propionate.

Topics: Acetates; Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Cyclopropanes; Drug Therapy, Combination; Female; Fluticasone; Genotype; Humans; Male; Middle Aged; Polymorphism, Genetic; Quinolines; Receptors, Adrenergic, beta-2; Respiratory Function Tests; Salmeterol Xinafoate; Sulfides

Bronchial asthma is defined as "a chronic inflammatory disease of the airways involving many cells" and inhaled corticosteroids have therefore become the fundamental drugs for the long-term management of the disease. In moderate and severe persistent asthma the use of a long-acting bronchodilator is recommended in order to control symptoms and to enhance the efficacy of corticosteroids. Although not based on scientific evidence, it has been assumed that the, 2 adrenergic and the inhaled steroid should be administered in a strict inhalation sequence: the bronchodilatator first and then the steroid. The aim of the study was to assess the effects of this assumption experimentally, common indeed since long ago.. Twelve subjects with moderate-persistent asthma (7 males, aged 18-64, basal FEV1 = 65.59% pred. +/- 7.59 ds; reversibility = + 14.8% +/- 8.3 ds from baseline after Salbutamol 200mg), symptomatic despite the regular home treatment with Fluticasone p. 250mg bid and beta 2 short-acting prn for over 6 weeks, were initially treated with combined SM/FP 50/250mg bid from an unique Diskus" device, for 6 weeks. After this initial phase, the treatment continued according to a randomised, double-blind, cross-over design: all subjects received the same drugs, from two different Diskus" inhalers, and according to two different sequences of administration: 1) SM first and FP 20' later for 4 weeks, and then FP first and SM 20' later for a further 4 weeks; 2) vice versa. No wash-out period was included between these two phases of cross-over treatment. FEV1 (% pred.); morning PEF (L/min), the use of short-acting beta 2 as required (n/week); the number of awakenings at night (n/week), and the daytime asthma symptom score were measured.. The t paired test and anova (Duncan test) were used for statistical comparisons: a p<0.05 was accepted as the minimum level of significance.. After the first six weeks of treatment with combined Salmeterol/Fluticasone, 50/250 mg FEV1 changed from 69.6% pred. +/- 7.59 ds to 79.8% pred. +/- 10.1 ds (p>0.005), whilst the morning PEF changed from 282.2 l/min : 64.1 ds to 333.4 l/min +/- 55.5 ds (p<0.02). Furthermore, the consumption of beta 2 adrenergic prn dropped from 4.4 (no./week) +/- 7.3 ds to 1.2 +/- 0.9 ds (p<0.001); the number of night-time awakenings decreased from 1.6 (no./week) +/- 0.2 ds to 0.2 +/- 0.3 ds (p<0.001), and the daytime symptom score changed from 3.4 +/- ds 0.8 to 1.9 +/- 0.7 ds (p<0.001). This therapeutic performance was maintained over the two subsequent 4-week periods of treatment from two distinct devices independently of the inhalation sequence. In particular, by both using salmeterol first or using fluticasone first, the therapeutic effects proved quite identical: FEV1: 80.7 % pred. +/- 9.5 ds and 80.3 +/- 7.4 ds; morning PEF: 336.5 l/min +/- 55.4 ds and 338.6 l/min +/- 67.1 ds; consumption of beta 2 adrenergic as required: 0.9 (no./week) +/- 0.6 ds and 0.9 (no./week) +/- 0.8 ds; number of awakenings: 0.3 (no./week) +/- 0.3 and 0.2 (no./week) +/- 0.3 ds; day-time/night-time symptom score: 1.7 +/- 0.5 ds and 1.8 +/- 0.6 ds, respectively (anova = ns).. Both in terms of lung function and of clinical outcomes the efficacy of SM and FP administration proved completely independent of the particular sequence for their separate inhalation and quite superimposable to thatachieved b y their combined inhalation from an unique device.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Antagonists; Adrenergic beta-Antagonists; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Spirometry; Treatment Outcome

To evaluate the efficacy and tolerability of fluticasone propionate (FP) hydrofluoroalkane (HFA) in children age 1 to < 4 years with asthma.. Children were assigned (2:1) to receive FP HFA 88 mug (n = 239) or placebo HFA (n = 120) twice daily through a metered-dose inhaler with a valved holding chamber and attached facemask for 12 weeks. The primary efficacy measure was mean percent change from baseline to endpoint in 24-hour daily (composite of daytime and nighttime) asthma symptom scores.. The FP-treated children had significantly greater (P < or = .05) reductions in 24-hour daily asthma symptom scores (-53.9% vs -44.1%) and nighttime symptom scores over the entire treatment period compared with the placebo group. Daytime asthma symptom scores and albuterol use were slightly more decreased with FP than with placebo; however, the differences were not statistically significant. Increases in the percentage of symptom-free days were comparable. The percentage of patients who experienced at least 1 adverse event was similar in the 2 groups. Baseline median urinary cortisol excretion values were comparable between the groups, and there was little change from baseline at endpoint. FP plasma concentrations demonstrated that systemic exposure was low.. FP HFA 88 mug twice daily was effective and well tolerated in pre-school-age children with asthma.

Topics: Administration, Inhalation; Aerosol Propellants; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child, Preschool; Circadian Rhythm; Double-Blind Method; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Infant; Male; Metered Dose Inhalers; Treatment Outcome

Early asthmatic responses (EAR) and late asthmatic responses (LAR) to allergen are induced by the local release of a series of bronchoconstrictor mediators, including leukotrienes and histamine. Both anti-leukotrienes and other anti-asthma drugs, such as inhaled glucocorticoids, have been shown to reduce both EAR and LAR. The aim of the present study was to directly compare the effects of regular treatment with an oral anti-leukotriene, montelukast (Mont; 10 mg once daily, for 8 days), and an inhaled glucocorticoid [fluticasone propionate (FP) 250 microg twice daily for 8 days] on the EAR and LAR to an inhaled allergen challenge. Patients with a documented EAR and LAR at a screening visit were randomized to these treatments, or placebo, in a double-blind, double-dummy, crossover fashion. Allergen challenge at a dose causing both an EAR and LAR was given on the eighth day of treatment. The maximum fall in FEV1 during the EAR was 17.8% during placebo treatment, 8.3% during Mont and 16.3% during FP (P <0.05 for Mont vs placebo). The maximum fall during the EAR was 13.8% during placebo treatment, 11.8% during Mont and 2% during FP treatment (P <0.05 for FP vs placebo and FP vs Mont). PC20 methacholine was significantly higher 24 h after allergen challenge during FP-treatment compared with Mont (P <0.05). Both montelukast and fluticasone reduced the relative amount of sputum eosinophils after allergen compared with placebo treatment. This study shows that anti-leukotrienes are effective to attenuate the EAR, whereas inhaled glucocorticoids are more effective than anti-leukotrienes in attenuating the EARs and improves bronchial hyperresponsiveness to a greater extent. In conclusion, inhaled glucocorticoids have overall greater efficacy than oral anti-leukotrienes to attenuate allergen-induced airway responses in mild asthmatic patients.

Topics: Acetates; Adult; Allergens; Androstadienes; Asthma; Bronchial Provocation Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Methacholine Chloride; Quinolines; Sputum; Sulfides; Time Factors

This study assessed the effects of treatment with fluticasone in children younger than 2 years old with recurrent wheezing and risk factors of developing asthma. This double-blind placebo-controlled study randomized children to receive fluticasone (125 mug; n = 14) or placebo (n = 12) twice daily for 6 months. Pulmonary function was assessed at the beginning and end, and parents filled out a daily diary recording respiratory symptoms, need for rescue medication, and emergency care. The SD score of maximum flow at functional residual capacity was -0.74 +/- 0.6 at the beginning and 0.44 +/- 1 at the end for the fluticasone group (p = 0.001), and -0.79 +/- 0.3 at the beginning and -0.78 +/- 1.4 at the end for the placebo group (p = 0.97). A statistically significant difference (p = 0.02) was observed between treatments. The percentage of symptom-free days was 91.3 +/- 7% for fluticasone and 83.9 +/- 10% for placebo (p = 0.05). The number of respiratory exacerbations was 2.1 +/- 1.7 and 4.1 +/- 3 (p = 0.04), and the percentage of days on albuterol was 8.6 +/- 6% and 16.3 +/- 9% (p = 0.028). Treatment with fluticasone twice daily for 6 months improves pulmonary function and clinical outcomes in children with asthma younger than 2 years.

Topics: Androstadienes; Asthma; Bronchodilator Agents; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Infant; Male; Respiratory Function Tests; Respiratory Sounds; Risk Factors; Time Factors

Ciclesonide is a novel inhaled corticosteroid that is converted in the lungs to its active metabolite, desisobutyryl-ciclesonide (des-CIC). The aim of this study was to compare the deposition of ciclesonide, as well as its conversion to des-CIC, in the oropharyngeal cavity with fluticasone propionate (FP) following inhalation via hydrofluoroalkane-propelled metered-dose inhalers (HFA-MDIs). Eighteen asthmatics inhaled ciclesonide 800 microg followed by FP 1000 microg or vice versa in an open, randomized, 2-treatment, 2-sequence study design. The oropharynx was washed out immediately and at 15, 30, 45, and 60 minutes after inhalation. Samples were analyzed for ciclesonide, des-CIC, and FP using liquid chromatography with tandem mass-spectrometric detection. Concentration-time curves and area under the concentration-time curve (AUC) were calculated for each drug. Ciclesonide and FP were recovered in almost all samples. Within 60 minutes after inhalation, the amounts of both ciclesonide and FP decreased sharply, and low residual levels were detected after 30 minutes. des-CIC was detected in relatively low concentrations, with maximum concentration 30 minutes following inhalation. The AUC(0-60 min) for ciclesonide (250.4 nmol x h/L) and des-CIC (37.8 nmol x h/L) were found to be significantly lower compared with FP (636.2 nmol.h/L, P < .001). Approximately 50% less ciclesonide and 90% less metabolite were present in the oropharynx compared with FP. Less than 20% of the residual ciclesonide in the oropharynx was metabolized to des-CIC. These findings indicate that oropharyngeal deposition of ciclesonide is only half that of FP following inhalation from an HFA-MDI. Furthermore, there is little activation of ciclesonide to its active metabolite in the oropharynx, suggesting a decreased likelihood of inhaled ciclesonide-associated oropharyngeal side effects.

Topics: Administration, Inhalation; Adult; Androstadienes; Area Under Curve; Asthma; Chromatography, Liquid; Cough; Drug Administration Schedule; Ethanol; Female; Fluticasone; Humans; Male; Mass Spectrometry; Metered Dose Inhalers; Oropharynx; Pregnenediones; Solutions; Therapeutic Irrigation; Time Factors

Inhaled corticosteroids (ICSs) are an effective treatment of asthma even when administered at a low dose. Once asthma is controlled, current guidelines recommend that the dose of ICS be reduced to the lowest possible and effective dose. Although the most appropriate strategy for the stepping down has not yet been defined, quantification of sputum eosinophils and bronchial hyperresponsiveness (BHR) are indeed measures of asthma control.. To compare the efficacy of step-down and fixed-dose strategies in the control of BHR to methacholine and eosinophilic inflammation patients with mild-to-moderate asthma.. We performed a double-blind, randomized study to compare inhaled fluticasone propionate (FP), 1,000 microg/d, then reduced to 200 microg/d (group 1; n = 18) to a fixed dose of FP, 200 microg/d (group 2; n = 17) administered for 6 weeks and then 8 weeks in reducing the provocative dose of methacholine causing a 20% fall in FEV1 (PD20) and sputum eosinophils in 35 patients. The duration of the efficacy was also followed subsequently after 8 weeks of placebo treatment.. PD20 remarkably increased with both treatment strategies, but differences between groups were not significant. Sputum eosinophils (median values, percentage) at baseline and after each treatment period were not different (group 1, 16.4 to 1.0 to 2.7%; group 2, 16.7 to 2.8 to 2.8%, respectively). The percentages of patients in whom sputum eosinophilia was normalized (< or = 3%) were as follows: group 1, 69% and 60%; group 2, 50% and 57%. After placebo treatment, sputum eosinophils were still "normalized" in approximately one third of patients.. Step-down and fixed-dose strategies with FP improved PD20 and sputum eosinophilia to a similar degree. The effect on sputum eosinophils persisted longer than that on methacholine.

Topics: Adolescent; Adult; Androstadienes; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Cell Count; Double-Blind Method; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Sputum; Vital Capacity

Inhaled corticosteroids and leukotriene receptor antagonists reduce airway eosinophilia and have been used as first line anti-inflammatory therapy for mild persistent asthma.. A multicentre, randomised, placebo controlled, parallel group study was performed to compare the anti-inflammatory effects of fluticasone propionate and montelukast as measured by sputum eosinophils in 50 adults with symptomatic steroid naive asthma and sputum eosinophilia of > or =3.5%.. Eighteen patients received low dose fluticasone (250 mug/day), 19 received montelukast (10 mg/day), and 13 were given placebo for 8 weeks. Fluticasone treatment resulted in a greater reduction in sputum eosinophils (geometric mean (SD) 11.9 (2.3)% to 1.7 (5.1)%) than montelukast (10.7 (2.3)% to 6.9 (3.8)%; p = 0.04) or placebo (15.4 (2.4)% to 7.8 (4.2)%; p = 0.002), and improvement in FEV(1) (mean (SD) 2.6 (0.9) l to 3.0 (0.9) l) than montelukast (2.8 (0.7) l to 2.8 (0.9) l; p = 0.02) or placebo (2.4 (0.8) l to 2.4 (0.9) l; p = 0.01). Treatment with fluticasone suppressed sputum eosinophilia within a week while montelukast only attenuated it. The effect of montelukast was maximal at 1 week and was maintained over 4 weeks. The effect of fluticasone was maintained over 8 weeks while that of montelukast was not.. Montelukast is not as effective as low dose fluticasone in reducing or maintaining an anti-inflammatory effect in steroid naive eosinophilic asthma.

Topics: Acetates; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Cyclopropanes; Double-Blind Method; Eosinophils; Female; Fluticasone; Humans; Leukotriene Antagonists; Male; Patient Compliance; Pulmonary Eosinophilia; Quinolines; Sputum; Sulfides; Treatment Outcome

Responses to inhaled corticosteroids (ICSs) and leukotriene receptor antagonists (LTRAs) vary among asthmatic patients.. We sought to determine whether responses to ICSs and LTRAs are concordant for individuals or whether asthmatic patients who do not respond to one medication respond to the other.. Children 6 to 17 years of age with mild-to-moderate persistent asthma were randomized to one of 2 crossover sequences, including 8 weeks of an ICS, fluticasone propionate (100 microg twice daily), and 8 weeks of an LTRA, montelukast (5-10 mg nightly depending on age), in a multicenter, double-masked, 18-week trial. Response was assessed on the basis of improvement in FEV 1 and assessed for relationships to baseline asthma phenotype-associated biomarkers.. Defining response as improvement in FEV 1 of 7.5% or greater, 17% of 126 participants responded to both medications, 23% responded to fluticasone alone, 5% responded to montelukast alone, and 55% responded to neither medication. Compared with those who responded to neither medication, favorable response to fluticasone alone was associated with higher levels of exhaled nitric oxide, total eosinophil counts, levels of serum IgE, and levels of serum eosinophil cationic protein and lower levels of methacholine PC(20) and pulmonary function; favorable response to montelukast alone was associated with younger age and shorter disease duration. Greater differential response to fluticasone over montelukast was associated with higher bronchodilator use, bronchodilator response, exhaled nitric oxide levels, and eosinophil cationic protein levels and lower methacholine PC(20) and pulmonary function values.. Response to fluticasone and montelukast vary considerably. Children with low pulmonary function or high levels of markers associated with allergic inflammation should receive ICS therapy. Other children could receive either ICSs or LTRAs.

Topics: Acetates; Administration, Inhalation; Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Eosinophil Cationic Protein; Eosinophils; Exhalation; Female; Fluticasone; Forced Expiratory Volume; Humans; Immunoglobulin E; Leukocyte Count; Male; Nitric Oxide; Predictive Value of Tests; Quinolines; Sulfides; Vital Capacity

Some studies have demonstrated that the function of the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis is significantly impaired in patients with oral corticosteroid (CS)-induced osteoporosis. The aim of study was to investigate the effects of long-term therapy with inhaled CSs (ICSs) on the hypothalamic-pituitary-GH axis by the GH response to GH-releasing hormone (GHRH), as well as bone turnover, in adult asthmatic patients.. Cross-sectional study.. Twenty-seven adult subjects with mild-to-moderate persistent asthma (long-term ICS therapy [ie, > 1 year], 20 patients; naive to ICS treatment, 7 patients) and 10 control subjects.. Each subject underwent testing with an IV bolus (1 mug/kg) injection of human GHRH, and samples of GH were taken 15 min before the GHRH injection, at 0 min (ie, at the time of GHRH injection), and at 15, 30, 45, 60, and 90 min after injection to obtain values for peak GH and DeltaGH. At baseline, samples of serum IGF-1 and blood-urine were collected for bone turnover markers.. The GH response to GHRH was significantly reduced in asthmatic patients receiving ICSs (peak GH, p < 0.05; and DeltaGH, p < 0.01) in comparison with control subjects and asthmatic patients who were naive to ICS therapy (peak GH and DeltaGH, p < 0.01). Baseline IGF-1 levels were similar in the three groups. Serum osteocalcin, a marker of bone formation, was significantly reduced (p < 0.01) and correlated with GH peak (r(2) = 0.34; p = 0.007) in asthmatic patients who were treated with ICSs.. We conclude that GH secretion in response to GHRH is significantly reduced in adult asthmatic patients receiving therapy with ICS and that such inhibition could play a negative role in bone metabolism.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bone Density; Bone Remodeling; Budesonide; Cross-Sectional Studies; Female; Fluticasone; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Long-Term Care; Male; Middle Aged; Osteocalcin; Statistics as Topic

The present study aimed to investigate whether a fixed combination of salmeterol and fluticasone (SFC) from a single inhaler provides sufficient asthma control comparable to that achieved with standard treatment (inhaled steroid in a dose of 1,000 mcg BDP- (beclomethasone dipropionate) equivalent plus a LABA and/or theophylline and/or montelukast).. In a prospective, randomised study patients with moderate or severe asthma were either switched to a twice daily inhalation of 50 mcg salmeterol plus 500 mcg fluticasone from the Viani forte 50/500 mcg Diskus (n = 142 patients), or they were maintained on standard treatment (n = 89 patients). If adequate asthma control was achieved after 8 weeks, the dose of the inhaled steroid was reduced by 50 % during weeks 9 to 16.. After 8 weeks, 81 % of the patients who had been switched to SFC and 80 % of patients on standard treatment achieved sufficient asthma control. After reducing the ICS dose by 50 %, asthma control remained appropriate in 90 % of SFC-patients, but only in 75 % of patients receiving standard treatment (p = 0.031). In addition, asthma symptoms and use of rescue medication were significantly more stable in SFC patients (p < 0.05).. With the salmeterol fluticasone combination product, patients with moderate asthma can achieve a control of their asthma, which is as good as that after standard treatment. In most SFC patients the fluticasone dosage can be reduced by 50 % without losing asthma control.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Reproducibility of Results; Respiratory Function Tests; Salmeterol Xinafoate

Several studies published in the second half of the 1990s have shown a therapeutic early effect of inhaled corticosteroids in acute asthma. However, systemic corticosteroids are considered the standard of care.. To compare the effect of repeated doses of inhaled fluticasone with the standard treatment of systemic corticosteroids in adult patients with severe acute asthma.. One hundred six patients (mean age, 33.5 +/- 8.8 years) were randomly assigned to receive fluticasone (3,000 microg/hour) administered through a metered-dose inhaler and spacer at 10-minute intervals for 3 hours, or 500 mg of intravenous hydrocortisone. In addition, all patients received inhaled albuterol and ipratropium bromide.. Subjects treated with fluticasone showed 30.5 and 46.4% greater improvements in PEF and FEV1, respectively, compared with the hydrocortisone group. The fluticasone group had better PEF and FEV1 at 120, 150, and 180 minutes (p < 0.05). Also, the fluticasone group showed higher rates of patients who obtained the discharge threshold at 90, 120, and 150 minutes. This therapeutic benefit was particularly evident in those patients with the most severe obstruction. Subjects with a baseline FEV1 of less than 1 L treated with fluticasone showed a significant increase in pulmonary function (p = 0.001) and a significant decrease in hospitalization rate (p = 0.05).. The use of repeated doses of inhaled fluticasone was more effective than intravenous hydrocortisone and was associated with an early improvement. This therapeutic benefit was particularly evident in those patients with the most severe obstruction.

Topics: Acute Disease; Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; Hydrocortisone; Injections, Intravenous; Male; Respiratory Function Tests; Treatment Outcome

There are no data comparing the relative effects of high-dose ciclesonide (CIC) and fluticasone propionate (FP) on airway and systemic outcomes in patients with moderate persistent asthma.. We elected to evaluate the relative effects of CIC and FP on the plasma cortisol response to stimulation with human corticotropin-releasing factor (hCRF) and bronchial hyperresponsiveness to methacholine as the primary outcome variables, in addition to secondary outcomes of overnight 10-h urinary cortisol (OUC) levels, exhaled nitric oxide levels, lung function, symptoms, and quality of life.. Fourteen patients with moderate persistent asthma (mean FEV(1), 67% predicted [prior to each randomized treatment]) completed the study, which had a randomized, double-blind, double-dummy, crossover design, per protocol. Patients stopped receiving their usual inhaled corticosteroids for the duration of the study and instead began receiving salmeterol, 50 mug twice daily, and montelukast, 10 mg once daily, for the 2-week washout periods prior to each randomized treatment, in order to prevent dropouts after withdrawal from inhaled corticosteroid therapy. Patients received 4 weeks of either CIC, 200 microg ex-valve (160 microg ex-actuator) four puffs twice daily, plus FP-placebo, four puffs twice daily, or FP, 250 microg ex-valve (220 microg ex-actuator) four puffs twice daily, plus CIC-placebo, four puffs twice daily. Salmeterol and montelukast were withheld for 72 h prior to each postwashout baseline visit, and CIC or FP was withheld for 12 h prior to each posttreatment visit.. FP, but not CIC, when compared to respective baseline values, significantly suppressed (p < 0.05) plasma cortisol levels as follows: FP prior to receiving hCRF: geometric mean fold difference, 1.2; 95% confidence interval (CI), 1.1 to 1.3; CIC prior to receiving hCRF: geometric mean fold difference, 0.9; 95% CI, 0.8 to 1.0; FP 30 min after receiving hCRF: geometric mean fold difference, 1.2; 95% CI, 1.1 to 1.3; CIC 30 min after receiving hCRF: geometric mean fold difference, 1.0; 95% CI, 0.9 to 1.2; OUC after FP administration: geometric mean fold difference, 1.9; 95% CI, 1.4 to 2.6; OUC after CIC administration: geometric mean fold difference, 1.2; 95% CI, 0.9 to 1.5. There was also a significantly lower (p < 0.05) mean value for OUC levels after FP administration than after CIC administration (geometric mean fold difference, 1.5; 95% CI, 1.1 to 2.0). Therapy with CIC and FP, compared to respective baselines, significantly increased (p < 0.05) the provocative concentration of methacholine causing a 20% fall in FEV(1), as follows: CIC: doubling dilution difference, 0.8; 95% CI, 0.1 to 1.6; FP: doubling dilution difference, 1.0; 95% CI, 0.1 to 2.0. It also significantly reduced (p < 0.05) exhaled nitric oxide levels, as follows: CIC: geometric mean fold difference, 1.2; 95% CI, 1.1 to 1.3; FP: geometric mean fold difference, 1.9; 95% CI, 1.3 to 2.8. There was no effect on other secondary efficacy outcomes.. FP, 2,000 microg daily, but not CIC, 1,600 microg daily, significantly suppressed hypothalamic-pituitary-adrenal axis outcomes, with OUC levels being lower after FP administration than after CIC administration. Both drugs significantly improved airway outcomes in terms of methacholine bronchial hyperresponsiveness and exhaled nitric oxide levels. The present results would therefore suggest that CIC might confer a better therapeutic ratio than FP when used at higher doses.

Topics: Administration, Inhalation; Androstadienes; Asthma; Breath Tests; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Corticotropin-Releasing Hormone; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Methacholine Chloride; Middle Aged; Nitric Oxide; Peak Expiratory Flow Rate; Pregnenediones; Quality of Life; Spirometry

Treatment with inhaled steroids is an effective method of reducing bronchoconstriction and airway inflammation after allergen challenge. However, the duration of the protective effects of inhaled steroids after discontinuation of therapy has not been established.. We sought to evaluate the protective effect of 1 week of inhaled steroid therapy against inhaled allergen challenge 12 hours after discontinuation of therapy.. In this randomized, double-blind, placebo-controlled crossover trial, 26 asthmatic subjects (>18 years old) not using inhaled steroids were administered 200 microg of budesonide twice daily, 200 microg of fluticasone twice daily, or placebo twice daily for 1 week. Twelve hours after discontinuation of therapy, subjects were administered an inhaled allergen challenge. Each treatment period was separated by a 3-week washout period.. When compared with placebo (26% +/- 14%), there was a slight but significant protection against the allergen-induced early response after fluticasone treatment (19% +/- 10%, P = .001) but not after budesonide treatment (23% +/- 13%, P = .08). However, when the area under the curve for the early airway response was examined, there was no difference between the 2 drugs in the amount of protection ( P = .62). Partial protection was demonstrated against the late-response allergen-induced sputum eosinophilia with both treatments ( P = .001). By contrast, no protection was observed against allergen-induced airway hyperresponsiveness for either treatment.. The protective effects of inhaled steroids against allergen-induced early responses, airway eosinophilia, and allergen-induced airway hyperresponsiveness are partially or completely lost as early as 12 hours after discontinuation of therapy.

Topics: Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Budesonide; Eosinophils; Female; Fluticasone; Humans; Male; Middle Aged; Time Factors

The duration of bronchodilator action of the long-acting beta agonist salmeterol when administered in the evening has not been investigated. In this study we have investigated whether a single evening dose of salmeterol, administered from the combination salmeterol/fluticasone (SFC) Accuhaler significantly attenuates the circadian rhythm in airway tone over 24 h.. Eighteen subjects with mild to moderate asthma (mean FEV1 84% predicted) participated in a double-blind, double dummy, placebo controlled, cross-over study. Subjects inhaled, in random order, placebo, salbutamol (200 microg) or SFC (50/100 microg) administered in the evening (2000 h) on three separate occasions. Lung function measurements including FEV1, specific airways conductance (sGaw) and maximum expiratory flow at 25-75% of vital capacity (MEF(25-75%)) were assessed at baseline, at 1 h and subsequently every 4 h post-dose for 24 h.. Compared with placebo, SFC significantly improved the three measures of airways function throughout the 24 h period, with a difference in FEV1 at 24 h of 0.24 l (0.00-0.47 l). SFC abolished the biphasic pattern of the circadian rhythm in airway tone. In contrast, salbutamol had a significant bronchodilator action of 4-8 h, depending on the lung function parameter measured.. The single evening administration of SFC via the Accuhaler resulted in a duration of bronchodilation of at least 24 h, with the abolition of the accentuated biphasic circadian variation in airway tone observed in asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Circadian Rhythm; Drug Administration Schedule; Drug Combinations; Epidemiologic Methods; Female; Fluticasone; Humans; Male; Middle Aged; Respiratory Function Tests; Salmeterol Xinafoate

To evaluate the efficacy and the safety of low dose salmeterol/fluticasone (SM/FP) combination therapy as compared to morate dose of budesonide (BUD) in the management of adult asthma.. A multicentre, randomised, open-label, parallel-group, 6-week treatment study was conducted. 398 patients (18 - 70 years) were given SM/FP (50/100 microg) twice daily via Accuhaler or BUD 400 microg twice daily via Turbuhaler.. The morning and the evening peak expiratory flow (PEF) measurements both increased significantly (P < 0.01) in the SM/FP group, and the increase was greater than that in the BUD group. The significant benefit of SM/FP was evident from the first week. SM/FP led to a more significant reduction in the use of rescue medication and in the day- and night-time asthma symptom scores, as compared to budesonide. Both treatments were well tolerated, and the adverse reactions showed no significant difference between the two groups.. Combination use of low doses of SM/FP is a better choice for the control of asthma. The addition of a low-dose long-acting beta(2) agonist is superior to the simple increase of the dosage of inhaled corticosteroids.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Powders; Salmeterol Xinafoate; Treatment Outcome; Young Adult

Despite their proven efficacy in the treatment and prevention of asthma exacerbations, current inhaled corticosteroids carry safety concerns, especially adrenal suppression. Ciclesonide (hydrofluoroalkane propellant) is a novel inhaled corticosteroid with few, if any, clinical adverse events.. To evaluate the potential effects of ciclesonide therapy on the dynamic cortisol response to sequential low- and high-dose cosyntropin stimulation in adults with mild-to-moderate persistent asthma.. This was a double-blind, randomized, placebo-controlled, 12-week study in adults with mild-to-moderate asthma. One hundred sixty-four patients were randomized and treated; 148 patients completed the study. Fluticasone propionate (chlorofluorocarbon propellant) was used as an active comparator. The doses administered were 320 microg of ciclesonide once daily, 320 microg of ciclesonide twice daily, and 440 microg of fluticasone propionate twice daily, all doses ex-actuator.. For both ciclesonide groups, changes in mean low- and high-dose peak serum cortisol levels and in 24-hour urinary free cortisol levels corrected for creatinine were small vs baseline and comparable with placebo. For the fluticasone propionate group, significant reductions vs placebo in serum cortisol levels in response to high-dose cosyntropin stimulation and in 24-hour urinary free cortisol levels were observed. Oral candidiasis rates were 2.5% for 320-microg/d ciclesonide, 2.4% for 640-microg/d ciclesonide, and 22.0% for 880-microg/d fluticasone propionate.. These findings confirm the safety of ciclesonide therapy, demonstrating that at doses up to 640 microg/d, the drug does not affect sensitive markers of adrenal function.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Cosyntropin; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Patient Compliance; Pituitary-Adrenal System; Pregnenediones

Subjects with atopic asthma often experience a disappearance of symptoms around puberty. However, airway inflammation and remodeling may persist. It is unknown whether those findings warrant prolonged anti-inflammatory treatment despite the absence of symptoms. In this study, we investigated whether a short course of combined anti-inflammatory treatment would, also in this specific patient population, diminish airway inflammation and/or remodeling.. A double-blind, randomized placebo-controlled trial was conducted in 28 asymptomatic subjects with a history of atopic asthma, with established bronchial hyperresponsiveness to methacholine (MCh) as non-invasive indicator of ongoing airway pathology.. Intervention consisted of the salmeterol/fluticasone propionate combination (SFC) product (50/250 microg bid via the Diskus inhaler) or placebo for 3 months.. The change in lung function (FEV1), bronchial response to MCh and adenosine monophosphate (AMP), the fraction of nitric oxide in exhaled air (FENO) and quality of life (QOL) scores were measured. Also, bronchial biopsies were taken and cryo sections immunostained for eosinophils (major basic protein, MBP) and mast cells (tryptase and chymase) before and after treatment. The change in reticular basement membrane (RBM) thickness, one of the parameters of airway remodeling, was also determined.. SFC treatment improved hyperresponsiveness to MCh (P = 0.014) as well as AMP (P = 0.011), and reduced FENO (P < 0.001) significantly as compared with placebo. Lung function tended to improve (NS). Furthermore, SFC treatment reduced tryptase in the subepithelium of bronchial biopsy specimens (P = 0.01), and slightly reduced RBM thickness (P = 0.05). However, eosinophils in (sub)epithelium were not significantly affected; neither were chymase levels, blood eosinophils or QOL scores.. We found that 3 months of treatment with fluticasone propionate and salmeterol reduced airway hyperresponsiveness, FENO and tryptase density in the airway mucosa as markers of airway inflammation. MBP density in the airway mucosa and QOL were, however, unchanged. The clinical relevance of these findings, especially with respect to the long-term outcome, has not been determined yet.

Topics: Adolescent; Adult; Albuterol; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Breath Tests; Bronchial Hyperreactivity; Bronchoscopy; Double-Blind Method; Female; Fluticasone; Humans; Male; Nebulizers and Vaporizers; Nitric Oxide; Respiratory Function Tests; Salmeterol Xinafoate; Treatment Outcome

Qvar Autohaler efficacy on asthma control, assessed with E. Juniper asthma control questionnaire (ACQ), was compared with fluticasone and budesonide. An open randomized study, stratified (2:1) on the intake of long-acting beta2-mimetics (LAbeta2), was performed in patients with moderate to severe poorly controlled asthma (defined by at least one nocturnal discomfort in the last 5 days or a mean of 2 puffs of short-acting beta2-mimetics in the last 7 days or exercise dyspnea) despite treatment with beclomethasone < or = 1000 microg/day (or equivalent). 460 patients received Qvar Autohaler 800 microg/day (n = 149), fluticasone Diskus 1000 microg/day (n = 149) or budesonide Turbuhaler 1600 microg/day (n = 162) during 12 weeks. Asthma control improved in all groups, with no difference between groups. For patients treated with LAbeta2 (n = 286) a significantly greater improvement of the ACQ score was obtained with Qvar Autohaler versus fluticasone (1.0 +/- 1.0 vs. 0.6 +/- 0.9; P = 0.019), but not versus budesonide (0.9 +/- 0.9). Pulmonary function test improvements were similar in the 3 groups. The significant improvement in asthma control in patients receiving LAbeta2 suggests potential advantages for extrafine aerosols as part of anti-inflammatory treatment optimization.

Topics: Administration, Inhalation; Adult; Aerosols; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Administration Schedule; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Leukotriene Antagonists; Male; Metered Dose Inhalers; Middle Aged; Particle Size; Peak Expiratory Flow Rate; Respiratory Function Tests; Salmeterol Xinafoate

The initial management of patients who present with persistent respiratory symptoms includes recognizing those with the potential to benefit from inhaled steroid therapy. To date, this has required undertaking a "trial of steroid" to identify responders. There is increasing evidence that steroid response is more likely in patients with eosinophilic airway inflammation, and this can be assessed indirectly using exhaled nitric oxide (FENO) measurements.. We aimed to assess the predictive accuracy of FENO to identify steroid response in 52 patients presenting with undiagnosed respiratory symptoms in a single-blind, fixed-sequence, placebo-controlled trial of inhaled fluticasone for 4 weeks.. Comparisons of predictive accuracy were made between FENO and other conventional predictors: peak flows, spirometry, bronchodilator response, and airway hyperresponsiveness measured at baseline. "Steroid response" was defined as change in symptoms, peak flows, spirometry, or airway hyperresponsiveness to adenosine based on established guidelines and recommendations.. Steroid response was significantly greater in the highest FENO tertile (> 47 ppb) for each endpoint. This outcome was independent of the diagnostic label. The predictive values for FENO were significantly greater than for almost all other baseline predictors, with an optimum cut point of 47 ppb.. FENO measurements greater than 47 ppb provide a means of predicting steroid response in patients with undiagnosed respiratory symptoms. Assessing airway inflammation is of more practical value than diagnostic labeling when considering the potential usefulness of inhaled antiinflammatory therapy.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Female; Fluticasone; Humans; Male; Nitric Oxide; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Single-Blind Method

International guidelines for the treatment of asthma recommend adjusting the dose of inhaled corticosteroids on the basis of symptoms, bronchodilator requirements, and the results of pulmonary-function tests. Measurements of the fraction of exhaled nitric oxide (FE(NO)) constitute a noninvasive marker that may be a useful alternative for the adjustment of inhaled-corticosteroid treatment.. In a single-blind, placebo-controlled trial, we randomly assigned 97 patients with asthma who had been regularly receiving treatment with inhaled corticosteroids to have their corticosteroid dose adjusted, in a stepwise fashion, on the basis of either FE(NO) measurements or an algorithm based on conventional guidelines. After the optimal dose was determined (phase 1), patients were followed up for 12 months (phase 2). The primary outcome was the frequency of exacerbations of asthma; the secondary outcome was the mean daily dose of inhaled corticosteroid.. Forty-six patients in the FE(NO) group and 48 in the group whose asthma was treated according to conventional guidelines (the control group) completed the study. The final mean daily doses of fluticasone, the inhaled corticosteroid that was used, were 370 microg per day for the FE(NO) group (95 percent confidence interval, 263 to 477) and 641 microg per day for the control group (95 percent confidence interval, 526 to 756; P=0.003), a difference of 270 microg per day (95 percent confidence interval, 112 to 430). The rates of exacerbation were 0.49 episode per patient per year in the FE(NO) group (95 percent confidence interval, 0.20 to 0.78) and 0.90 in the control group (95 percent confidence interval, 0.31 to 1.49), representing a nonsignificant reduction of 45.6 percent (95 percent confidence interval for mean difference, -78.6 percent to 54.5 percent) in the FE(NO) group. There were no significant differences in other markers of asthma control, use of oral prednisone, pulmonary function, or levels of airway inflammation (sputum eosinophils).. With the use of FE(NO) measurements, maintenance doses of inhaled corticosteroids may be significantly reduced without compromising asthma control.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Algorithms; Androstadienes; Asthma; Biomarkers; Breath Tests; Bronchodilator Agents; Child; Eosinophils; Female; Fluticasone; Humans; Leukocyte Count; Male; Middle Aged; Nitric Oxide; Prospective Studies; Single-Blind Method; Spirometry; Sputum

We aimed to evaluate the efficacy and safety of fluticasone propionate (FP) in children aged 12-47 months with recurrent/persistent asthma symptoms. One hundred and sixty children (12-47 months) were randomised into this multicentre, double-blind, placebo-controlled, parallel-group study, and treated with either FP (100 microg bd) or placebo (2 puffs bd), both administered by metered-dose-inhaler and Babyhaler for 12 weeks. The primary endpoint was percentage of symptom-free 24h periods. Over weeks 1-12, FP-treated patients had significantly more percentage symptom-free 24-h periods compared with placebo (odds ratio 0.53; 95% CI 0.29-0.95; P = 0.035). Relative to baseline, where all patients were symptomatic for at least 21/28 days of the run-in, the improvement equated to one additional symptom-free 24 h period per week. FP patients also had a significantly higher percentage of 24 h periods with no wheeze or cough, the odds ratio for treatment difference corresponding to two additional wheeze-free and one additional cough-free periods per week. FP was well-tolerated, with similar reported adverse events in both groups. Urinary cortisol-creatinine ratio was slightly decreased among FP patients after 12 weeks, but with no clinical correlates. FP is effective for the treatment of chronic persistent asthma symptoms in very young children.

Topics: Administration, Inhalation; Androstadienes; Asthma; Bronchodilator Agents; Child, Preschool; Cough; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Infant; Male; Odds Ratio; Recurrence; Respiratory Sounds

To determine whether montelukast is as effective as fluticasone in controlling mild persistent asthma as determined by rescue-free days.. Participants aged 15 to 85 years with mild persistent asthma (n = 400) were randomized to oral montelukast (10 mg once nightly) or inhaled fluticasone (88 mug twice daily) in a year-long, parallel-group, multicenter study with a 12-week, double-blind period, followed by a 36-week, open-label period.. The mean percentage of rescue-free days was similar between treatments after 12 weeks (fluticasone: 74.9%, montelukast: 73.1%; difference = 1.8%, 95% confidence interval [CI]: -3.2% to 6.8%) but not during the open-label period (fluticasone: 77.3%, montelukast: 71.1%; difference = 6.2%, 95% CI: 0.8% to 11.7%). Although both fluticasone and montelukast significantly improved symptoms, quality of life, and symptom-free days during both treatment periods, greater improvements occurred with fluticasone in lung function during both periods and in asthma control during open-label treatment. Post hoc analyses revealed a difference in rescue-free days favoring fluticasone in participants in the quartiles for lowest lung function and greatest albuterol use at baseline.. In patients with mild persistent asthma, rescue-free days and most asthma control measures improved similarly with fluticasone or montelukast over the short term, but with prolonged open-label treatment, asthma control improved more with fluticasone. Improved asthma control with fluticasone appeared to occur in those with decreased lung function and greater albuterol use at baseline. In the remaining patients, the two treatments appeared to be comparable. These results suggest that classification criteria for mild persistent asthma may need to be re-evaluated.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Androstadienes; Anti-Asthmatic Agents; Asthma; Cyclopropanes; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Humans; Quinolines; Sulfides; Treatment Outcome

A patient-driven, adjustable maintenance dosing (AMD) approach to asthma therapy, in which the dose is adjusted by patients according to the severity of their symptoms, has recently been compared with fixed-dose therapy in open-label studies.. This study used a double-blind, double-dummy design to compare the efficacy of 2 treatment approaches: stable dosing of salmeterol/fluticasone propionate (SAL/FP) and AMD of formoterol/budesonide (FOR/BUD).. This was a 1-year, multicenter, randomized, double-blind, double-dummy study in adult patients with symptomatic asthma that was not controlled by therapy with 200 to 500 microg/d inhaled corticosteroid (ICS) plus a long-acting beta2 agonist, or with >500 to 1000 microg/d ICS alone. Patients were randomized to receive 1 inhalation of SAL/FP 50/250 microg BID or 2 inhalations of FOR/BUD 6/200 microg BID, both delivered via dry powder inhaler devices. After 4 weeks of stable dosing in both groups, eligible patients continued the study for an additional 48 weeks, receiving either a stable dose of SAL/FP or AMD of FOR/BUD. According to the AMD treatment plan, patients initially halved their dose and subsequently stepped up or down as indicated by the presence or absence of nocturnal awakenings due to asthma, frequency of rescue medication use, and changes in morning peak expiratory flow (PEF). The primary end point was the percentage of symptom-free days. Other parameters included daily asthma symptom scores, morning PEF, percentage of days free of rescue medication use, daily rescue medication use, percentage of nighttime awakenings due to asthma, percentage of weeks with well-controlled asthma, and number of exacerbations requiring oral corticosteroids or emergency department (ED) visits/hospitalizations. Tolerability was assessed in terms of adverse events spontaneously reported or elicited at clinic visits.. The intent-to-treat population comprised 688 patients (344 per treatment arm) with a mean age of 45 years and a mean baseline forced expiratory volume in 1 second 81% of the predicted normal value. After 4 weeks' stable dosing, 581 patients (295 SAL/FP, 286 FOR/BUD) continued beyond visit 3 into the remaining 48-week treatment period. Over weeks 1 through 52, patients receiving stable dosing of SAL/FP had a significantly greater percentage of symptom-free days compared with those receiving AMD of FOR/BUD (median, 58.8% vs 52.1%, respectively; P = 0.034). The incidence of asthma exacerbations requiring oral steroids or an ED visit/hospitalization was 47% lower with SAL/FP compared with FOR/BUD (adjusted annual mean rate, 0.18 vs 0.33; P = 0.008). During weeks 5 through 52, patients in the FOR/BUD AMD group used a mean of 1.8 inhalations/d (equivalent to BUD 360 microg/d), and 235 (82.2%) patients stepped down to 1 inhalation/d. Mean (SD) daily ICS exposure over 52 weeks was 463 (81) microg FP and 480 (238) microg BUD in the respective treatment arms.. In this adult population with persistent asthma, stable dosing of SAL/FP 50/250 microg BID resulted in significantly greater increases in symptom-free days, days free of rescue medication, and morning PEE, as well as almost halving the exacerbation rate, compared with AMD of FOR/BUD 6/200 microg. The results suggest that there is a minimum daily amount of maintenance therapy necessary to prevent exacerbations in adults with persistent asthma.

Topics: Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Salmeterol Xinafoate; Self Administration; Treatment Outcome

Studies suggest that nasal treatment might influence lower airway symptoms and function in patients with comorbid rhinitis and asthma. We investigated the effect of intranasal, inhaled corticosteroid or the combination of both in patients with both pollen-induced rhinitis and asthma.. A total of 262 patients were randomized to 6 weeks' treatment with intranasal fluticasone propionate (INFP) 200 microg o.d., inhaled fluticasone propionate (IHFP) 250 microg b.i.d., their combination, or intranasal or inhaled placebo, in a multicentre, double-blind, parallel-group study. Treatment was started 2 weeks prior to the pollen season and patients recorded their nasal and bronchial symptoms twice daily. Before and after 4 and 6 weeks' treatment, the patients were assessed for lung function, methacholine responsiveness, and induced sputum cell counts.. Intranasal fluticasone propionate significantly increased the percentages of patients reporting no nasal blockage, sneezing, or rhinorrhoea during the pollen season, compared with IHFP or intranasal or inhaled placebo. In contrast, only IHFP significantly improved morning peak-flow, forced expiratory volume in 1 second (FEV1) and methacholine PD20, and the seasonal increase in the sputum eosinophils and methacholine responsiveness.. In patients with pollen-induced rhinitis and asthma, the combination of intranasal and IHFP is needed to control the seasonal increase in nasal and asthmatic symptoms.

Topics: Administration, Inhalation; Administration, Intranasal; Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Asthma; Comorbidity; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Pollen; Rhinitis, Allergic, Seasonal; Treatment Outcome

The efficacy and systemic effects of ciclesonide, a novel glucocorticosteroid, inhaled via pressurized metered-dose inhaler (pMDI) were compared with fluticasone propionate pMDI in 26 patients with asthma, using a randomized, double blind, placebo-controlled, double dummy, 6-period crossover study design. Treatments were placebo, ciclesonide 320 microg (ex-actuator dose) once daily (o.d.), ciclesonide 640 microg o.d., ciclesonide 640 microg twice daily (b.i.d.), fluticasone propionate 440 microg (ex-actuator dose) b.i.d., and fluticasone propionate 880 microg b.i.d. The primary variable was area under the plasma cortisol concentration-time curve over 24 h (plasma cortisol AUC(0-24), relative to placebo) derived from samples taken every 2 h, on the 9th day of treatment. Secondary variables were 24-h urinary cortisol excretion and PC20 for adenosine 5'-monophosphate (AMP) (relative to placebo and expressed in doubling concentrations). Ciclesonide did not affect 24-h cortisol secretion. Fluticasone propionate suppressed cortisol secretion as demonstrated by a decrease in plasma cortisol AUC(0-24), relative to placebo, by 29% (95% CI 15-41) and 59% (95% CI 51-66) with 440 and 880 microg b.i.d., respectively. PC20 more than doubled with each active treatment, but no statistically significant dose-response effect could be established. It was concluded that moderate to high doses of fluticasone propionate suppressed cortisol secretion, that ciclesonide did not suppress cortisol secretion, and that all active treatments decreased hyperresponsiveness to AMP.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adolescent; Adult; Androstadienes; Area Under Curve; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Hydrocortisone; Lung; Male; Middle Aged; Pregnenediones; Spirometry; Treatment Outcome

Deep inspiration-induced bronchoprotection and bronchodilation are impaired in asthma. We evaluated the effect of inhaled glucocorticosteroids on these phenomena. Two groups of subjects with asthma, 9 with moderate/severe hyperresponsiveness to methacholine, and 12 with mild/borderline hyperresponsiveness to methacholine, received inhaled fluticasone (880 microg daily) for 12 weeks. Serial bronchoprovocations were performed at Weeks 0, 6, and 12. The impact of deep inspirations on the airway response to methacholine was evaluated on the basis of inspiratory vital capacity and FEV(1). Fluticasone produced a wide spectrum of changes in the beneficial effects of deep inspiration, but the mean changes were not significant. The magnitude of the steroid-induced changes in bronchoprotection by deep inspiration correlated with baseline log PC(20) (the provocative concentration of methacholine causing a 20% fall in FEV(1); higher log PC(20) predicted improvement of the deep inspiration effect). The steroid-induced changes led to the emergence of strong positive correlations between the effects of deep inspiration and the methacholine log PC(20) that did not exist at baseline. We conclude that deep inspiration-induced bronchoprotection can be restored by inhaled glucocorticosteroids only in individuals with mild hyperresponsiveness. After steroid treatment, the beneficial effects of deep inspiration become significant determinants of the magnitude of airway hyperresponsiveness.

Topics: Administration, Inhalation; Adult; Aged; Androstadienes; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Female; Fluticasone; Forced Expiratory Volume; Humans; Inhalation; Male; Methacholine Chloride; Middle Aged; Respiratory Mechanics; Respiratory Therapy; Severity of Illness Index; Vital Capacity

A randomised, open-label, multicentre study compared the efficacy and tolerability of salmeterol 25 microg/fluticasone propionate 125 microg (two puffs, twice daily) delivered via a hydrofluoroalkane metered-dose inhaler (HFA-MDI) and salmeterol 50microg/fluticasone propionate 250 microg (one puff, twice daily) delivered via a Diskus inhaler in Chinese patients with moderate asthma uncontrolled with inhaled corticosteroids (ICSs). Morning peak expiratory flow (PEF) was the primary efficacy endpoint. Secondary endpoints included evening PEF, forced expiratory volume in 1 s, day and night symptom scores, rescue medication and patient self-evaluation of efficacy. Safety was assessed according to adverse events recorded. Both treatments were equipotent and significantly improved morning PEF (HFA-MDI 40 l/min; Diskus 42 l/min; p < 0.05) and all secondary endpoints (p < 0.05) from baseline, over 1-4 weeks. Similarly, both treatments were well tolerated. Salmeterol/fluticasone propionate delivered via an HFA-MDI or Diskus inhaler provides a choice of efficacious delivery systems in Chinese patients whose asthma is poorly controlled on ICSs alone.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aerosol Propellants; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Treatment Outcome

Lung function is commonly used as the primary endpoint in asthma clinical trials, but it may not reflect changes which are important to patients. The present study compared changes in, and relationships between, traditional and patient-centred end-points during treatment with three classes of asthma medication. Subjects with mild-to-moderate asthma were randomised to double-blind, double-dummy crossover treatment with eformoterol 12 microg b.i.d. or montelukast 10 mg q.d., then single-blind treatment with fluticasone 250 microg b.i.d./placebo capsules, with 6-week treatment periods and 1-week washouts. Individual "traditional" end-points (symptoms, reliever use, forced expiratory volume in one second per cent predicted, morning peak expiratory flow, airway hyperresponsiveness) and "patient-centred" end-points (asthma control questionnaire, quality of life, patient global assessments) were assessed. Principal component analysis and linear modelling were used to explore overall rank orders for treatment, and relationships between outcomes. A total of 58 subjects were randomised. The rank order of benefit from eformoterol and fluticasone differed for three factors derived from principal component analysis (eformoterol>fluticasone for symptom/reliever use factor, fluticasone>eformoterol for lung function factor, eformoterol=fluticasone for patient-centred factor). Montelukast was ranked third for all three factors. A significant relationship between patient-based variables and lung function was found only for montelukast treatment. In asthma treatment, traditional end-points do not fully capture patient-centred benefits, and the relationship between end-points differs with medication class.

Topics: Acetates; Adolescent; Adult; Aged; Androstadienes; Asthma; Cross-Over Studies; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Ethanolamines; Female; Fluticasone; Follow-Up Studies; Forced Expiratory Volume; Formoterol Fumarate; Humans; Linear Models; Male; Middle Aged; New South Wales; Patient Satisfaction; Patient-Centered Care; Probability; Quality of Life; Quinolines; Respiratory Function Tests; Severity of Illness Index; Single-Blind Method; Sulfides; Treatment Outcome

Inflammation in asthma extends into the small airways (< 2 mm diameter). Most inhaled corticosteroids are suspensions with a particle size > 2 mm. Therefore, inflammation in the small airways of patients with asthma may not be adequately treated with these preparations. Some inhaled corticosteroids, on the other hand, are compounded with alcohol, resulting in a solution producing an aerosol that has a mean particle diameter of < 2 mm. This study was designed to compare the addition of equivalent amounts of two inhaled corticosteroids (one a suspension and one a solution) to the treatment of patients with asthma, which was uncontrolled despite treatment with moderate to high doses of inhaled corticosteroids and usually additional controller medications. The study was performed with 30 patients, > or = 18 years of age. Subjects were randomized in a single-blind fashion to receive, in addition to their current asthma therapy, either CFC-FP 220 microg each morning and 110 microg each evening (n = 10) or HFA-BDP 160 mcg twice daily (n = 20). Pre- and postbronchodilator spirometry, single breath nitrogen washout for closing volume and residual volume by plethysmography were assessed before and after 3 months of therapy. In the subjects who received HFA-BDP, the ratio of closing volume (CV) to vital capacity (VC) and residual volume (RV) decreased significantly (p = 0.0214 and 0.0433, respectively), whereas forced expiratory flow over 25-75% of the vital capacity (FEF25-75%), forced expiratory volume in 1 second (FEV1), and morning peak flow improved significantly (p = 0.0014, 0.0184, and 0.0321). Improvements from baseline of CV, CV/VC, and postbronchodilator FEF25-75%, were statistically significant in the HFA-BDP group compared with the CFC-FP group (p = 0.0049, 0.0194, and 0.0355, respectively). These preliminary findings suggest that the addition of HFA-BDP, compared with CFC-FP in patients with poorly controlled asthma despite receiving moderate to high doses of inhaled steroids, has a greater effect on parameters reflecting small airway patency presumably secondary to reduction in inflammation.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; Bronchodilator Agents; Chlorofluorocarbons; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Pharmaceutical Solutions; Pulmonary Ventilation; Single-Blind Method; Suspensions

Guidelines recommend daily controller therapy for mild persistent asthma. Montelukast has demonstrated consistent benefit in controlling symptoms of asthma and may be an alternative, orally administered, nonsteroidal agent for treating mild asthma.. The Montelukast Study of Asthma in Children (MOSAIC study) was a 12-month, multicenter, randomized, double-blind, noninferiority trial to determine the effect of once-daily, orally administered montelukast (5 mg) (n = 495), compared with twice-daily, inhaled fluticasone (100 microg) (n = 499), on the percentage of asthma rescue-free days (RFDs) (any day without asthma rescue medication and with no asthma-related resource use). Patients 6 to 14 years of age had mild persistent asthma (average percentage of predicted forced expiratory volume in 1 second: 87.2%; RFDs at baseline: 64%). Montelukast would be considered not inferior to fluticasone if the upper limit of the 95% confidence interval for the difference in mean percentages of RFDs (fluticasone minus montelukast) was above -7% (a difference of approximately 2 days/month).. The mean percentage of RFDs was 84.0% in the montelukast group and 86.7% in the fluticasone group. The least-squares mean difference was -2.8% (95% confidence interval: -4.7% to -0.9%), within the noninferiority limit of -7%. The proportion of patients requiring systemic corticosteroids and the number of patients with an asthma attack were greater in the montelukast group. Both montelukast and fluticasone were well tolerated.. Montelukast was demonstrated to be not inferior to fluticasone in increasing the percentage of RFDs among 6- to 14-year-old patients with mild asthma. Secondary end points, including percentage of predicted forced expiratory volume in 1 second value, days with beta-receptor agonist use, and quality of life, improved in both groups but were significantly better in the fluticasone treatment group.

Topics: Acetates; Administration, Inhalation; Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Cyclopropanes; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides

For children older than 5 years with asthma who remain symptomatic despite inhaled corticosteroid (ICS) therapy, the preferred treatment is to add an inhaled long-acting beta2-agonist vs increasing the ICS dose.. To compare the safety of twice-daily treatment with inhaled fluticasone propionate plus the inhaled long-acting beta2-agonist salmeterol with that of fluticasone propionate used alone in children aged 4 to 11 years with persistent asthma.. A randomized, multicenter, double-blind, active-controlled, parallel-group study in 203 children with persistent asthma who were symptomatic during ICS therapy. Patients received fluticasone propionate-salmeterol (100/50 microg) or fluticasone propionate (100 microg) alone twice daily for 12 weeks.. The safety profile of fluticasone propionate-salmeterol was similar to that of fluticasone propionate alone. The overall incidence of adverse events was 59% for fluticasone propionate-salmeterol and 57% for fluticasone propionate. Both treatments were well tolerated. Two patients receiving fluticasone propionate-salmeterol and 5 receiving fluticasone propionate withdrew from the study because of worsening asthma. Changes in heart rate, blood pressure, and laboratory variables were infrequent and were similar between treatments. No patients had clinically significant abnormal electrocardiographic findings during treatment. Geometric mean 24-hour urinary cortisol excretion at baseline and after 12 weeks of treatment was comparable within and between groups; no patient in either group had abnormally low 24-hour urinary cortisol excretion after 12 weeks of treatment. The incidence of withdrawals due to asthma exacerbations was 2% in the fluticasone propionate-salmeterol group and 5% in the fluticasone propionate group.. In pediatric patients with persistent asthma, fluticasone propionate-salmeterol twice daily was well tolerated, with a safety profile similar to that of fluticasone propionate used alone.

Topics: Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Blood Pressure; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Electrocardiography; Female; Fluticasone; Heart Rate; Humans; Hydrocortisone; Male; Salmeterol Xinafoate

To compare the effects of nebulized fluticasone propionate (FP) and nebulized budesonide (BUD) in addition to inhaled salbutamol in children with mild asthma exacerbation.. The study was a multicenter, randomized, single-blind, parallel group design. One hundred and sixty-eight children, aged 4-15 years, were randomly allocated to receive either nebulized FP (250 mcg) or nebulized BUD (500 mcg) twice daily for 10 days. On presentation, at the end of treatment, and after a 7-day follow-up, clinical assessment and pulmonary function measurements were performed. Daytime and nighttime asthma symptom scores, the use of rescue salbutamol, and morning/evening peak expiratory flow (PEF) values were recorded at home during the treatment period. Morning cortisol concentration (51 children) and overnight urinary cortisol excretion (30 children) were also measured in six centers at the start and at the end of the treatment.. Improvement of morning PEF was significantly higher in patients treated with FP (p=0.032). The percentage of symptom-free nights was significantly higher in the BUD group (p=0.006), but no difference was found in symptom-free days. No intergroup difference was detected in the percentage of days/nights free from rescue medication and in pulmonary function tests performed in outpatient settings. There was no evidence of hypothalamo-pituitary-adrenal axis suppression.. A short course of nebulized FP has the same effects as a double dose of nebulized BUD, when either drug is added to bronchodilator therapy in children with mild asthma exacerbation

Topics: Adolescent; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Circadian Rhythm; Drug Administration Schedule; Female; Fluticasone; Humans; Male; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Respiratory Function Tests; Severity of Illness Index; Single-Blind Method

The measure of inflammatory cytokines in the exhaled breath condensate has been recently proposed for use in monitoring asthma and the therapeutic response to steroids. The aim of the present study was to investigate the usefulness of measuring exhaled IL-6, IL-4 and pH in mild persistent asthma. Furthermore the effects on these markers of inhaled steroids were assessed. The study enrolled 28 asthmatic (15 males, 38+/-12 years) and 15 healthy subjects (5 males, 35+/-6 years). IL-6, IL-4 and pH were measured in the exhaled breath condensate of the subjects studied. Significantly higher concentrations of IL-6 and IL-4 were observed in the breath condensate of asthmatic patients (7.1+/-1.1 and 64.4+/-8.3 pg/ml) compared to controls (2.7+/-0.6 and 31.7+/-3.5 pg/ml), p<0.001. Furthermore, exhaled IL-4 fell significantly after treatment with inhaled steroids for 6 months (47.9+/-3.2 pg/ml, p<0.001) while exhaled IL-6 did not (6.4+/-1.0 pg/ml, p=0.8). The exhaled pH turned out to be lower in asthmatic subjects than in controls (7.39+/-0.11 vs. 7.85+/-0.14; P<0.001) but trended towards control levels after steroid treatment (7.65+/-0.16, P<0.001). We conclude that the measurement of exhaled IL-4 and pH in mild asthmatic subjects could be a useful way of monitoring their airway inflammation as well as their response to the treatment.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Biomarkers; Breath Tests; Female; Fluticasone; Humans; Hydrogen-Ion Concentration; Interleukin-4; Interleukin-6; Male; Middle Aged; Monitoring, Physiologic; Reproducibility of Results

To evaluate efficacy, safety, health outcomes, and cost-effectiveness of fluticasone propionate (FP) versus montelukast (MON) in 342 children (6 to 12 years of age) with persistent asthma.. Randomized, double-blind, 12-week study of treatment with FP inhalation powder 50 mug twice daily or MON chewable 5 mg once daily for 12 weeks.. Compared with MON, FP significantly increased mean percent change from baseline FEV1 (forced expiratory volume in 1 second) (P=.002), morning PEF (peak expiratory flow) (P=.004), evening PEF (P=.020), and percent rescue-free days (P=.002) at end point, and it significantly reduced nighttime symptom scores (P <.001) and mean total (P=.018), and nighttime (P <.001) albuterol use. Withdrawals from the study were more frequent with MON (21%) than with FP (13%). Adverse events (69% vs 71%) and mean end point to baseline 12-hour urinary cortisol excretion ratios were similar. Parents and physicians were more satisfied with FP treatment than with MON (P=.006 and P=.016, respectively, at Week 12). Mean total daily asthma-related cost per patient in the FP group was approximately one-third of that in the MON group ($1.25 vs $3.49).. FP was significantly more effective than MON in improving pulmonary function, asthma symptoms, and rescue albuterol use. Both therapies had similar safety profiles. Parent- and physician-reported satisfaction ratings were higher with FP treatment, and asthma-related costs were lower.

Topics: Acetates; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Cyclopropanes; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Quinolines; Respiratory Function Tests; Severity of Illness Index; Sulfides; Treatment Outcome

Inhaled corticosteroids (ICSs) reduce local airway inflammation, which is an underlying cause of asthma symptoms. However, potential systemic side effects associated with ICS use are a major concern for asthmatic patients.. Adult patients (n = 60; > or = 18 years of age) with moderate-to-severe asthma were randomized to receive 4 weeks of treatment with ciclesonide (CIC), 320 microg bid (CIC 640), CIC, 640 microg bid (CIC 1280), fluticasone propionate (FP), 440 microg bid (FP 880), FP 880 microg bid (FP 1760), or placebo (PBO) [all doses expressed as ex-actuator; comparable to ex-valve doses of 800 and 1,600 microg/d for CIC and 1,000 and 2,000 microg/d for FP, respectively].. After 29 days of treatment, CIC 640, CIC 1280, and FP 880 had no significant effect on the mean serum cortisol area under the curve for 0 to 24 h (AUC0-24h). FP 1760 produced a statistically significant suppression in mean serum cortisol AUC0-24h compared to PBO (p = 0.0009; 95% confidence interval [CI] -117.5 [corrected] to -32.1). Results obtained with cosyntropin stimulation revealed no statistically significant differences among the groups. The CIC 640 group demonstrated a significant increase compared to the PBO group in 24-h urinary cortisol levels from baseline at week 4 (p = 0.0224; 95% CI, 0.0023 to 0.0283), while the other treatment groups revealed no change in this parameter. The incidence of treatment-emergent adverse events was similar in all groups, and all adverse events were mild or moderate in severity.. Treatment with moderate and high doses of CIC does not result in hypothalamic-pituitary-adrenal-axis suppression as compared with PBO.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Cosyntropin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Hormones; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Pregnenediones

Inhaled glucocorticoids (GCs) are the most effective control therapy for asthma. Although the clinical effects of inhaled GCs vary, there are few data on the differences in the responsiveness of individuals to inhaled GCs. The purpose of this study was to identify those factors that are associated with responsiveness to high-dose inhaled GCs in patients with moderate-to-severe asthma.. This study was a prospective analysis.. Outpatient clinics of tertiary hospitals.. Eighty-six adult outpatients with moderate-to-severe asthma.. Eighty-six patients with asthma who had initial FEV1 values of < 80% predicted after they had received inhaled GCs (fluticasone propionate, 1,000 microg/d) for 4 weeks. The primary end points were FEV1, FEV1/FVC ratio, forced expiratory flow (midexpiratory phase), and the score at presentation in the asthma-related quality-of-life questionnaire (AQLQ).. The inhalation of GCs for 4 weeks had significant improvements in the FEV1% predicted and in the AQLQ score compared with the baseline values. Asthmatic patients with responses of > 12% (n = 46, 53.4%) in the change in FEV1 (deltaFEV1 = [FEV1 at 4 weeks--baseline FEV1]/baseline FEV1 x 100) also had significantly higher proportions of blood eosinophils and lower FEV1 values (in liters) prior to treatment. The change in FEV1 values correlated with the number of sputum eosinophils prior to GC inhalation (r = 0.242; p < 0.05) and correlated inversely with the FEV1 percent predicted values prior to GC inhalation (r = -0.462; p < 0.001).. The FEV1 percent predicted and the blood and sputum eosinophil levels prior to GC inhalation are associated with the responsiveness to inhaled GCs in patients with moderate-to-severe asthma.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Eosinophils; Fluticasone; Glucocorticoids; Humans; Middle Aged; Prospective Studies; Quality of Life; Remission Induction; Respiratory Function Tests; Treatment Outcome

We previously showed that H1-antihistamines may shift the PC20 (provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20%) threshold to adenosine monophosphate (AMP) challenge but may paradoxically prolong recovery.. To measure AMP recovery using a constant predetermined AMP PC20 and to evaluate whether fexofenadine use confers add-on effects to treatment with either fluticasone propionate alone or combined fluticasone propionate-salmeterol.. Fourteen atopic patients with mild-to-moderate asthma (forced expiratory volume in 1 second of 76%) completed a double-blind, randomized, crossover study consisting of 3-week treatment blocks of either fluticasone propionate-salmeterol, 250 microg twice daily, or fluticasone propionate alone, 250 microg twice daily, in conjunction with either fexofenadine, 180 mg once daily, or matched placebo. Recovery after a predetermined AMP PC20 challenge was measured (primary outcome), along with exhaled nitric oxide levels, plasma eosinophil cationic protein levels, peripheral eosinophil counts, pulmonary function, diary card outcomes, and quality of life (all secondary outcomes).. There were no differences in any of the primary or secondary outcomes when fexofenadine was added to treatment with either fluticasone propionate-salmeterol or fluticasone propionate alone. The mean AMP recovery time was 25.0 vs 23.4 minutes for fexofenadine and placebo, respectively, as add-on to fluticasone-salmeterol and 22.5 vs 23.9 minutes, respectively, as add-on to fluticasone alone.. Fexofenadine did not affect recovery to a fixed dose of AMP challenge or any other surrogate inflammatory markers when given as add-on therapy to corticosteroid-treatedatopic asthmatic patients.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Anti-Allergic Agents; Asthma; Biomarkers; Bronchial Provocation Tests; Drug Therapy, Combination; Eosinophil Cationic Protein; Eosinophils; Female; Fluticasone; Humans; Hypersensitivity, Immediate; Inflammation; Male; Nitric Oxide; Respiratory Function Tests; Salmeterol Xinafoate; Terfenadine; Treatment Outcome

In this study, the percentage of patients with uncontrolled asthma who can achieve guideline-defined asthma control was assessed in 3,421 patients. Significantly more patients (71%) treated with salmeterol-fluticasone achieved asthma control than did patients receiving fluticasone alone (59%). The patients treated with salmeterol-fluticasone achieved asthma control more rapidly and at a lower dose of inhaled corticosteroid than did patients treated with fluticasone alone. Achievement of asthma control was associated with marked improvements in exacerbation rates and quality of life. Thus guideline-defined asthma control can be achieved in the majority of patients and should be the goal of asthma treatment.

Topics: Adrenal Cortex Hormones; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Therapy, Combination; Fluticasone; Humans; Practice Guidelines as Topic; Prospective Studies; Quality of Life; Salmeterol Xinafoate; Treatment Outcome

Asthma and allergic rhinitis are both highly prevalent diseases and often coexist in patients.. To investigate the effect of rhinitis therapy on asthma outcomes in adult and adolescent patients with both seasonal allergic rhinitis (SAR) and persistent asthma.. A total of 863 patients (mean baseline FEV1 81% predicted) were randomized to receive open-label fluticasone propionate/salmeterol (FSC), 100/50 microg bid for 4 weeks, plus either blinded fluticasone propionate aqueous nasal spray (FPANS) 200 microg/d, montelukast 10 mg/d, or placebo. Patients kept daily records of peak expiratory flow (PEF), asthma, and rhinitis symptoms and rescue albuterol use.. FPANS added to FSC resulted in superior outcomes for daytime total nasal symptom scores (D-TNSS) and individual daytime nasal specific symptoms (congestion, rhinorrhea, sneezing, and itching) compared with montelukast plus FSC and placebo plus FSC (p < or = 0.001). Montelukast plus FSC was superior to placebo plus FSC only for D-TNSS and itching and sneezing. Morning PEF, asthma symptoms, and rescue albuterol use improved significantly (p < or = 0.001) in all treatment groups, but improvements were comparable across the treatment groups.. In patients with persistent asthma treated with FSC, the addition of montelukast or FPANS for the treatment of SAR resulted in no additional improvements in overall asthma control compared with FSC alone. However, FPANS provided superior rhinitis control compared with montelukast. These data suggest that asthma and rhinitis should each be optimally treated.

Topics: Acetates; Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Cyclopropanes; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Patient Selection; Quinolines; Reproducibility of Results; Respiratory Distress Syndrome; Respiratory Function Tests; Rhinitis, Allergic, Perennial; Sleep Wake Disorders; Sulfides; Treatment Outcome; Wakefulness

This study aimed to compare the efficacy of nebulized therapy with salbutamol alone or in combination with fluticasone. In a randomized, double-blind clinical trial, 150 children with moderate acute asthma were randomly assigned to receive by nebulizations either (i) three doses of salbutamol 30 microl/kg per dose, each dose administered every 15 min, (ii) three doses of salbutamol plus two doses of fluticasone 500 microg/dose at 15 and 30 min after first dose of salbutamol, or (iii) three doses of salbutamol/fluticasone 500 microg/dose, each combined dose administered every 15 min. Pulse oxymetry (SaO2), peak expiratory flow (PEF) and Wood et al. (Am J Dis Child, 123, 1972, 123) clinical scale were evaluated at baseline, 15, 30, 45, 60, 90 and 120 min after the first nebulization. Patients in the three groups significantly improved since 15 min after the first nebulization. We did not observe differences in the recovery of SaO2 and PEF among the three groups of treatment (p > 0.10). In group 3, children showed better clinical response at 120 min than the other two groups (p < 0.05). No significant adverse effects were observed with any treatment. To summarize, in children with acute moderate asthma, nebulized salbutamol at an accumulated dose of 90 mul/kg plus fluticasone at an accumulated dose of 1500 microg produced better clinical relief after 2 h. However, similar PEF and SaO2 responses were observed with salbutamol alone or in combination with different doses of fluticasone.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Nebulizers and Vaporizers; Oxygen; Peak Expiratory Flow Rate; Time Factors

This 12-month dose-titration study assessed the effectiveness of budesonide/formoterol for maintenance plus relief with a control group using salmeterol/fluticasone for maintenance plus salbutamol for relief. Adolescents and adults (n = 2,143; mean forced expiratory volume in one second (FEV1) 73% predicted; mean inhaled corticosteroid (ICS) 884 microg.day(-1)) were randomised to budesonide/formoterol 160/4.5 microg two inhalations b.i.d. plus additional inhalations as needed, or salmeterol/fluticasone 50/250 microg b.i.d. plus salbutamol as needed. Treatment was prescribed open label; after 4 weeks, physicians could titrate maintenance doses in accordance with normal clinical practice. Maintenance plus as-needed budesonide/formoterol prolonged the time to first severe exacerbation versus salmeterol/fluticasone (25% risk reduction). The total number of severe exacerbations was significantly reduced in the budesonide/formoterol group (255 versus 329). Both regimens provided sustained improvements in symptoms, as-needed use, quality of life and FEV1, with differences in favour of the budesonide/formoterol group for as-needed use (0.58 versus 0.93 inhalations.day(-1)) and FEV1 (post-beta2-agonist values). Mean ICS dose during treatment was similar in both groups (653 microg budesonide.day(-1) (maintenance plus as-needed) versus 583 microg fluticasone.day(-1)). The simplified strategy using budesonide/formoterol for maintenance and reliever therapy is feasible, safe and at least as effective as salmeterol/fluticasone plus salbutamol.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Internationality; Male; Middle Aged; Patient Satisfaction; Prevalence; Prognosis; Quality of Life; Risk Assessment; Risk Factors; Salmeterol Xinafoate; Treatment Outcome

Adding a long-acting beta(2)-agonist to inhaled corticosteroids results in better symptomatic asthma control than increasing the dose of inhaled corticosteroids.. Investigating whether adding the long-acting beta(2)-agonist salmeterol to the inhaled corticosteroid fluticasone propionate has an effect on allergen-induced allergic inflammation in asthma.. Bronchial allergen challenges were performed in 26 patients with allergic asthma, pretreating them with a single dose of either fluticasone/salmeterol (100/50 microg) or fluticasone alone (100 microg), in a double-blind, randomized, cross-over design. Sputum and serum markers of bronchial inflammation were measured after allergen challenge, as well as lung function parameters. Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein.. Asthmatic responses after allergen challenge were significantly reduced after pretreatment with fluticasone/salmeterol relative to fluticasone alone. Sputum inflammatory markers after allergen challenge were not significantly affected by fluticasone/salmeterol pretreatment. By contrast, serum IL-5 was significantly reduced (geometric mean serum IL-5 [SEM]: 0.5 [0.3] vs 1.1 [0.3] pg/mL 1 hour and 0.6 [0.3] vs 1.1 [0.3] pg/mL 6 hours after challenge with fluticasone/salmeterol vs fluticasone alone pretreatment, respectively; P values < .05). Also, peripheral blood eosinophils were significantly reduced (geometric mean number x 10(6)/L [SEM]: 172 [0.1] vs 237 [0.1] at 6 hours and 271 [0.1] vs 351 [0.1] at 24 hours with fluticasone/salmeterol vs fluticasone alone pretreatment, respectively; P < .05).. Adding salmeterol to fluticasone reduces allergen-induced serum IL-5 and peripheral blood eosinophils. This phenomenon may contribute to the improved clinical outcomes that result from adding a long-acting beta(2)-agonist to inhaled corticosteroids.

Topics: Administration, Inhalation; Albuterol; Allergens; Androstadienes; Asthma; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Eosinophils; Fluticasone; Humans; Hypersensitivity; Interleukin-5; Leukocyte Count; Salmeterol Xinafoate; Time Factors

There has been concern that in allergic asthmatic patients there might be an interactive effect on inflammation between regular salmeterol use and exposure to allergens, resulting in increased airway responsiveness.. To determine the effects of salmeterol on allergen-induced changes in airway responsiveness and exhaled nitric oxide (ENO) levels in allergic asthmatic patients concomitantly taking inhaled corticosteroids.. Forty-two asthmatic patients sensitized to pollen allergens were randomly allocated to treatment with fluticasone propionate-salmeterol (n=21) or fluticasone propionate alone (n=21). Spirometry, the methacholine provocation concentration causing a 20% decline in forced expiratory volume in 1 second (PC20), the adenosine 5'-monophosphate (AMP) PC20, and ENO levels were measured before and at the height of the pollen season after 6 weeks of treatment.. Changes in the methacholine PC20, the AMP PC20, and ENO levels were not significantly different between treatment groups. No significant changes in the AMP PC20 were observed among the fluticasone propionate-salmeterol and fluticasone propionate groups during natural pollen exposure. However, a significant increase in the methacholine PC20 was observed in the fluticasone propionate-salmeterol group (P = .03) and in the fluticasone propionate group (P = .04); ENO concentrations decreased significantly in both groups during natural allergen exposure (P = .009 and .005).. In patients with pollen-induced asthma, treatment with either fluticasone propionate or fluticasone propionate-salmeterol is associated with significant reductions in methacholine responsiveness and ENO concentrations, even during natural pollen exposure. Furthermore, at least in patients with mild asthma, natural allergen exposure and the regular use of fluticasone propionate-salmeterol are not associated with a greater increase in ENO levels and airway responsiveness than natural allergen exposure and fluticasone propionate use alone.

Topics: Adenosine Monophosphate; Adolescent; Adult; Aged; Airway Resistance; Albuterol; Androstadienes; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Nitric Oxide; Seasons; Sulfonamides; Treatment Outcome

Asthma guidelines recommend increasing or doubling inhaled corticosteroid (ICS) dose to treat mild and moderate exacerbations of asthma in adults.. To: (i) compare the effectiveness of doubling existing daily ICS dose (fluticasone) with maintaining usual ICS dose and usual daily ICS dose accompanied by oral steroids (OS) (dexamethasone) during mild and moderately severe exacerbations of asthma in adults; (ii) examine determinants of success and failure; and (iii) compare side-effect profiles.. A randomized, double-blind, placebo-controlled (double-dummy), triple crossover trial. Participants acted as their own control. Outcome measures included treatment success/failure, peak expiratory flow (PEF) after 7 days therapy or at treatment failure, and side-effects.. From 22 participants (nine males and 13 females), 18 pairs of data were available for maintaining usual ICS versus doubling ICS and doubling ICS versus OS, and 19 for maintaining usual ICS versus OS. Median (fifth-95th percentile) age was 46.5 (32-64) years and forced expiratory volume in one second (FEV(1)) 73% (29-97%) predicted. The outcome after doubling ICS was not superior to maintaining usual ICS, with 11 (61%) failures in both arms (P = 0.66). OS, with only 5 (26%) failures, was superior to maintaining usual ICS with 12 (63%) failures (P = 0.04), and to doubling ICS with 5 (28%) versus 11 (61%) failures (P = 0.07). Median PEF (as percentage of run-in best) at end-points were 90.5% (57.1-177.1) for OS, 78.3% (39.5-103.1) for maintaining usual ICS and 77.9 (27.7-110.3) for doubling ICS. Neither gender nor PEF at exacerbation were predictive of failure. Although doubling ICS was not an effective therapy overall, ICS dose at exacerbation were predictive of success in the doubling ICS arm (P = 0.04). Treatment failures when doubling daily ICS dose were more common if achieved fluticasone dose was less than 2000 microg (three of 11, 73%) compared to 2000 microg or greater (eight of eight, 37.5%). Increasing age and the presence of an upper respiratory tract infection (URTI) were predictive of failure with OS. Side-effects were more commonly reported with OS (52.6%) than doubling ICS (42.1%) or maintaining usual ICS (19.1%) with the most common being mood changes (36.8%), sleep disturbance (31.6%) and changes in appetite (26.3%).. Doubling daily ICS dose per se is not effective for the treatment of mild to moderately severe exacerbations of asthma in adults. Success may depend on achieved ICS dose. Oral steroids are effective, but side-effects are common. A review of current guidelines may be warranted.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Cross-Over Studies; Dexamethasone; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Glucocorticoids; Humans; Logistic Models; Male; Middle Aged; Peak Expiratory Flow Rate; Prednisolone; Self Administration; Treatment Failure

In this randomized, double-blind, placebo-controlled trial, 397 patients with moderate to severe asthma, previously treated with bronchodilators alone, received fluticasone propionate 88, 220, or 440 microg twice daily, or placebo via metered dose inhaler (MDI) for 12 weeks. Mean change from baseline to endpoint in pre-dose percent predicted forced expiratory volume in one second (FEV1) was greater (p < 0.001) in each fluticasone propionate group (9.0%, 88 microg bid; 9.8%, 220 microg bid; 11.2%, 440 microg bid) versus placebo (3.4%). Morning and evening peak expiratory flow (PEF), asthma symptoms, and supplemental albuterol use also improved in all fluticasone propionate groups versus placebo. The incidence of adverse events and 24-hour urine cortisol excretion rates were similar between active treatments and placebo.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Aged, 80 and over; Androstadienes; Asthma; Bronchodilator Agents; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Metered Dose Inhalers; Middle Aged; Treatment Outcome

It is important to be able to compare the efficacy and systemic effects of inhaled corticosteroids but their slow onset of action makes it difficult to measure the maximum response to a given dose. Submaximal responses could be compared if the time course of action of the inhaled corticosteroids being compared was similar. We have compared the time course of action of fluticasone and budesonide, measuring response as change in the provocative dose of adenosine monophosphate causing a 20% fall in forced expiratory volume in 1 second (PD20AMP).. Eighteen subjects with mild asthma, aged 18-65, took part in a three way randomised crossover study. Subjects took fluticasone (1500 microg/day), budesonide (1600 microg/day), and placebo each for 4 weeks with a washout period of at least 2 weeks between treatments; PD20AMP and forced expiratory volume in 1 second (FEV1) were measured during and after treatment. The time taken to achieve 50% of the maximum response (T50%) was compared as a measure of onset of action.. There was a progressive increase in PD20AMP during the 4 weeks of treatment with both fluticasone and budesonide but not placebo; the increase after 1 and 4 weeks was 2.28 and 4.50 doubling doses (DD) for fluticasone and 2.49 and 3.65 DD for budesonide. T50% was 9.3 days for fluticasone and 7.5 days for budesonide with a median difference between fluticasone and budesonide of 0.1 days (95% CI -1.4 to 2.65). There was a wide range of response to both inhaled corticosteroids but good correlation between the response to fluticasone and budesonide within subjects. FEV1 and morning peak expiratory flow rate (PEFR) increased during the first week of both active treatments and were stable thereafter. There was a small progressive improvement in nocturnal symptoms with both active treatments.. PD20AMP was a more sensitive marker of response to inhaled corticosteroid therapy than FEV1 and PEFR. The time course of action of fluticasone and budesonide on PD20AMP is similar, suggesting that comparative studies of their efficacy using 1 or 2 week treatment periods are valid. When a new inhaled corticosteroid becomes available, a pilot study comparing its time course of action with that of an established corticosteroid should allow comparative studies to be performed more efficiently.

Topics: Administration, Inhalation; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Time Factors; Treatment Outcome

Our objective was to evaluate the efficacy and safety of two doses of fluticasone propionate (FP) in young children with recurrent wheezing and risk factors for asthma. Our study design was a randomized, double-blind, placebo-controlled comparison of inhaled FP 50 mcg twice daily (FP 100) and 125 mcg twice daily (FP 250), for 6 months. Outcome measures included number of wheezing episodes, days on albuterol, height standard deviation score (height SDS), osteocalcin (OC), bone alkaline phosphatase fraction (AKP), insulin-like growth factor-binding protein 3 (IGFBP-3), and serum levels of cortisol (SC). Our subjects were 30 patients, aged 7-24 months. Mean wheezing episodes were 6.0 +/- 1.9, 1.9 +/- 1.9, and 2.8 +/- 1.2; mean days of albuterol use were 24.3 +/- 1.3, 6.5 +/- 0.8, and 9.1 +/- 0.8, per patient for placebo, FP100, and FP250 groups, respectively. There was a significant reduction in clinical outcome in the two FP groups compared to placebo (P < 0.01). No significant correlations were found between FP dosage and height SDS, OC, AKP, IGFBP-3, and SC. In conclusion, in young children with asthmatic symptoms, FP at 50 and 125 mcg b.i.d. for 6 months significantly improved respiratory symptoms without causing significant side effects on growth and bone metabolism.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Asthma; Bone and Bones; Bronchodilator Agents; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Growth; Humans; Infant; Insulin-Like Growth Factor Binding Protein 3; Male; Recurrence; Respiratory Sounds; Treatment Outcome

Significant concern remains over the long-term side effects of inhaled steroids. This cross-sectional study evaluates the effect of high-dose inhaled fluticasone propionate (FP) on biochemical markers of bone metabolism and bone density in children with asthma. Children with chronic asthma using FP >/= 1,000 mcg daily for at least 6 months, and healthy controls, were entered in the study. No children had taken oral prednisolone within the previous month. Fasting morning serum was analyzed for bone formation markers, and spot urine for bone resorption markers. Dual-energy X-ray absorptiometry (DEXA) results were reviewed in a subgroup of patients. Forty-nine children with asthma and 32 controls were recruited. The mean FP dose was 771.2 +/- 253.35 mcg/m2/day. Unpaired t-test analysis revealed no significant difference in biochemical markers studied. In subjects with asthma; 13 of 37 (35.1%) had lumbar spine density more than one standard deviation below the mean (P = 0.001). This fell to 6/37 (16.2%) with bone age correction (NS). In conclusion, no significant reduction in bone metabolism or bone age-corrected bone mineral density was observed in children with asthma on prolonged high doses of inhaled FP.

Topics: Absorptiometry, Photon; Administration, Inhalation; Adolescent; Androstadienes; Asthma; Biomarkers; Body Mass Index; Bone and Bones; Bone Density; Bone Remodeling; Bronchodilator Agents; Child; Cross-Sectional Studies; Female; Fluticasone; Humans; Male; Osteocalcin; Steroids; Treatment Outcome

if patients with asthma remain symptomatic in spite of chronic treatment with inhaled corticosteroids (ICS), increasing the ICS dosage or adding another drug to the treatment regimen are possible therapeutic alternatives. We compared the efficacy and safety of combined salmeterol fluticasone therapy (SFC, 50/250 microg twice daily) with twice the dose of fluticasone propionate (FP, 500 microg b.i.d.) in symptomatic asthmatics.. this prospective, double-blind study was conducted in 76 study centres. 365 symptomatic patients with moderate asthma aged >18 years and receiving ICS in a dose equivalent to 1000 microg beclomethasone propionate per day were randomly assigned to receive either salmeterol xinafoate (50 microg) and fluticasone propionate (250 microg) in a single dry powder inhaler (Diskus) or 500 microg FP twice daily. The primary efficacy endpoint was morning peak expiratory flow rate (PEFR). Secondary measurements included forced expiratory volume in 1 second (FEV1), asthma symptom scores, and use of rescue medication.. combined salmeterol fluticasone therapy resulted in significantly greater improvements in PEFR and symptom control than doubling the dose of FP. At week 12, morning PEFR had increased by 52 L/min from baseline in patients on SFC and by 36 L/min in subjects receiving FP. The adjusted difference between groups was 16.6 L/min (95% confidence interval, 1.1 to 32.0 L/min). In the SFC group, the percentage of symptom-free days increased from baseline by 49% of days as compared with 38% of days after FP (adjusted difference: 12.6% of days, 95% CI 4.0 to 20.7). Quality of life improved to a greater degree after SFC therapy, and patients regarded study drugs as superior to their previous asthma medication. Adverse event profiles were similar between groups.. the combination of salmeterol 50 microg and fluticasone 250 microg in a single dry powder inhaler was superior to twice the dose of FP (500 microg). It seems justified to add salmeterol rather than increasing the ICS dose if symptomatic asthmatics require supplementary therapy.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Prospective Studies; Quality of Life; Salmeterol Xinafoate

Our aim was to compare the 12-month safety and efficacy of fluticasone propionate (FP) and sodium cromoglycate (SCG) in children aged 1 to 3 years with mild to moderate recurrent wheeze.. The study was a randomized, parallel-group, open-label multicenter study of 625 children, aged 1 to 3 years, with recurrent wheeze randomized in a 3:1 ratio to treatment for 52 weeks with FP (100 microg twice daily) via metered-dose inhaler and Babyhaler spacer device or SCG (5 mg 4 times daily) via metered-dose inhaler and Nebuhaler spacer device, respectively.. There was no significant difference in mean adjusted growth rates between the 2 groups: 84.0 mm/year in the FP group versus 86.4 mm/year in the SCG group (difference FP-SCG: -2.4 mm/year; 95% confidence interval: -6.6 to 1.8). Growth comparisons were independent of age, gender, previous use of steroid, or whether measured as length and/or height. Serum and urinary cortisol concentrations showed a statistically significant suppression of 10% and 14%, respectively, but the number of patients with serum cortisol levels below the lower normal limit was reduced during the trial. Both treatments were well tolerated. The most common drug-related adverse events were cough (2% FP vs 1% SCG) and hoarseness (1% FP vs 0% SCG). One incident of cataract was observed at baseline and 1 after FP treatment; the latter had resolved after 12 months. The efficacy of FP was superior to SCG with fewer cases of symptom worsening, exacerbations, and requirements for oral steroid treatment and more symptom-free days and days without use of rescue treatment.. Twelve months of treatment with inhaled FP (100 microg twice daily) in preschool children aged 1 to 3 years with recurrent wheeze has no effect on growth and no other clinically important side effects but is more efficacious than SCG.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Cataract; Child, Preschool; Cromolyn Sodium; Female; Fluticasone; Growth; Humans; Hydrocortisone; Infant; Male; Respiratory Sounds; Treatment Outcome

Cysteinyl-leukotrienes (cys-LTs) and 8-isoprostane are biomarkers of airway inflammation and oxidative stress.. The aim of this study was to evaluate cys-LT and 8-isoprostane levels in exhaled breath condensate (EBC) of children with different degrees of asthma severity.. EBC was collected from 14 steroid-naive children with mild persistent asthma, 13 children with stable mild- to-moderate persistent asthma treated with inhaled corticosteroids (ICS), 9 ICS-treated children with unstable asthma, and 19 healthy children.. In the three groups of asthmatic children, EBC concentrations of cys-LTs and 8-isoprostane were significantly higher than in control children (steroid-naive asthmatic children: cys-LTs median, 10.8 pg/mL, P <.001, 8-isoprostane, 16.2 pg/mL, P <.001; ICS-treated stable asthmatic children: cys-LTs, 12.7 pg/mL, P <.001, 8-isoprostane, 18.1 pg/mL, P <.001; children with unstable asthma: cys-LTs, 106.0 pg/mL, P <.01, 8-isoprostane, 29.7 pg/mL, P <.01; control children: cys-LTs, 4.3 pg/mL, 8-isoprostane, 3.5 pg/mL). Cys-LT levels were higher in children with unstable asthma than in the other two asthmatic groups (P <.05). FE(NO) levels were significantly higher in steroid-naive and in children with unstable asthma compared with ICS-treated children with stable asthma (P <.01).. Our study shows that EBC cys-LTs and 8-isoprostane concentrations are higher in asthmatic children than in healthy control children, with scattered values in patients with unstable asthma. These findings suggest that EBC eicosanoid measurement may have useful clinical implications for investigating phenotype differences among asthmatic patients.

Topics: Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Biomarkers; Breath Tests; Budesonide; Child; Cysteine; Dinoprost; F2-Isoprostanes; Female; Fluticasone; Forced Expiratory Volume; Humans; Leukotrienes; Male; Nitric Oxide; Oxidative Stress; Severity of Illness Index

Current asthma guidelines recommend that patients are educated to adjust their medication according to their asthma severity using physician-guided self-management plans. However, many patients take a fixed dose of their controller medication and adjust their reliever medication according to asthma symptoms.. This study examined whether asthma control improved if patients adjusted the maintenance dose of budesonide/formoterol (Symbicort Turbuhaler* 160/4.5 microg) according to asthma severity compared with traditional fixed dosing (FD) regimens.. Symptomatic patients with asthma (n = 658, mean symptom score 1.5, mean inhaled corticosteroids 735 microg/day, mean forced expiratory volume in 1 second [FEV(1)] 84% predicted) were randomised after 2 weeks' run-in to either: budesonide/formoterol adjustable maintenance dosing (AMD), budesonide/formoterol FD or salmeterol/fluticasone (Seretide Diskus dagger 50/250 microg) FD. In a 4-week double-blind period, both budesonide/formoterol AMD and FD groups received two inhalations twice daily (bid) and salmeterol/fluticasone FD patients received one inhalation bid. In the following 6-month open extension, both FD groups continued with the same treatment. Patients in the AMD group with well-controlled asthma stepped down to one inhalation bid; others continued with two inhalations bid. All AMD patients could increase to four inhalations bid for 7-14 days if symptoms worsened. All patients used terbutaline or salbutamol for symptom relief throughout. The primary variable was the odds of achieving a well-controlled asthma week (WCAW).. The odds ratio for achieving a WCAW did not differ between the FD regimens; however, during the open period, budesonide/formoterol AMD increased the odds of achieving a WCAW vs. budesonide/formoterol FD (odds ratio 1.335; 95% CI: 1.001, 1.783; p = 0.049) despite a 15% reduction in average study drug use. Budesonide/formoterol AMD patients had a lower exacerbation rate over the study: 40% lower vs. salmeterol/fluticasone FD (p = 0.018); 32% lower vs. budesonide/formoterol FD (NS). During the double-blind period, there were no clinically relevant differences between the budesonide/formoterol FD and salmeterol/fluticasone FD groups. Budesonide/formoterol AMD patients used less reliever medication in the open extension: 0.58 vs. 0.92 occasions/day for budesonide/formoterol FD (p = 0.001) and 0.80 occasions/day for salmeterol/fluticasone FD (p = 0.011).. Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control by reducing exacerbations and reliever medication usage compared with fixed-dose salmeterol/fluticasone.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Analysis of Variance; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Child; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Costs; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Pulmonary Ventilation; Salmeterol Xinafoate

The tulobuterol transdermal therapeutic system (TTS) is the world's first commercially available transdermal preparation of tulobuterol, a beta-2 stimulant, that can maintain effective blood tulobuterol levels for 24 hours when applied once daily. In the present study, a total of 36 adult patients with mildly persistent (Step 2) or moderately persistent (Step 3) bronchial asthma 19 who were using inhalational steroids and 17 who were not used tulobuterol TTS for one year and underwent measurement of peak expiratory flow (PEF) once daily. Peripheral eosinophil count, serum eosinophil cationic protein (ECP) level and airway responsiveness (Dmin) were evaluated at 6 months and 1 year after the start of the study. PEF exhibited significant improvements at 6 months and 1 year in patients treated with or without inhalational steroids, while serum ECP was improved significantly only in the patients on inhalational steroids. Patients not using inhalational steroids exhibited no significant exacerbation of Dmin at either 6 months or 1 year: One-year treatment with tulobuterol TTS did not appear to cause tachyphylaxis. The significant improvements in Dmin at 6 months and 1 year in the patients using inhalational steroids suggested that inhalational steroids offer beneficial effects in controlling airway inflammation. Tulobuterol TTS is considered quite beneficial in improving quality of life (QOL) in patients with bronchial asthma because its incidence of adverse effects including palpitations and shivering is significantly lower than those of oral preparations, because of its remarkable improvement of pulmonary function and symptoms of airway obstruction without increasing airway responsiveness even after repeated use, and because it is simple to use and offers excellent clinical efficacy.

Topics: Administration, Cutaneous; Administration, Inhalation; Adrenergic beta-Agonists; Aged; Androstadienes; Asthma; Beclomethasone; Bronchial Hyperreactivity; Delayed-Action Preparations; Drug Therapy, Combination; Female; Fluticasone; Humans; Inflammation; Male; Middle Aged; Peak Expiratory Flow Rate; Quality of Life; Severity of Illness Index; Terbutaline; Time Factors; Treatment Outcome

Asthma is associated with an increase in airway blood flow (Qaw), presumably as a manifestation of airway inflammation. We therefore determined the effect of the antiinflammatory agents montelukast (ML) and fluticasone propionate (FP) on Qaw in 12 patients with mild intermittent asthma. Using a double-blind approach, Qaw along with FEV(1) and Vmax(50) were determined before and after a 2-week treatment period with either ML (10 mg/day), FP (440 microg/day), or 10 mg of ML plus 440 microg of FP daily, separated by 2-week washout periods. Mean (+/- SEM) Qaw ranged from 68 +/- 4.2 to 71.8 +/- 5.9 microl x minute(-1) x ml(-1) anatomic dead space before the treatment periods. ML, FP, and ML plus FP decreased mean Qaw by 21.5, 20.8, and 26.9%, respectively (p < 0.05 for all). No significant difference was observed among the three regimens. FEV(1) and Vmax(50) were not changed by any of the treatments. We conclude that at the dosages used, ML and FP are equipotent in reducing Qaw in patients with mild asthma, and that the magnitude of the response is not greater if the two drugs are combined. The results also suggest that the vascular effects of these agents can be assessed independent of their effects on airway function.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Androstadienes; Asthma; Blood Flow Velocity; Bronchi; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Follow-Up Studies; Humans; Male; Middle Aged; Mucous Membrane; Multivariate Analysis; Probability; Pulmonary Circulation; Quinolines; Severity of Illness Index; Spirometry; Sulfides; Treatment Outcome

To evaluate the effects of treatment with fluticasone propionate vs placebo on bone, hypothalamic-pituitary-adrenal (HPA) axis function, and the eyes in patients with asthma.. This randomized, double-blind, placebo-controlled study of 160 patients with asthma who had minimal previous exposure to corticosteroids was conducted from July 1994 through June 1997. Patients received fluticasone at 88 microg twice daily, fluticasone at 440 microg twice daily, or placebo twice daily for 2 years. Bone mineral density (BMD) was evaluated every 6 months by lumbar spine, proximal femur, and total body scans. Measurements of HPA axis function and ophthalmic evaluations were conducted at similar intervals.. Among the 3 groups, no significant differences were observed in BMD at week 104 (at any anatomical site). Mean percent change from baseline in the lumbar spine was less than 1% for all 3 groups. At all time points, HPA axis function was similar in the 88-microg fluticasone group compared with the placebo group. For mean change from baseline in corticotropin-stimulated peak cortisol (P = .003 and P = .02 at weeks 24 and 52, respectively) and area under the stimulated plasma cortisol vs time curve (P = .002 and P = .02 at weeks 24 and 52, respectively), statistically significant reductions from baseline were observed in the 440-microg fluticasone group compared with the placebo group. These reductions of 10% to 13% from baseline were not accompanied by other signs of systemic effect and did not persist with continued treatment (at weeks 76 and 104). No important ocular changes were observed.. Long-term treatment with 88 microg of fluticasone twice daily was comparable to placebo in all skeletal, ophthalmic, and HPA axis function assessments. Treatment with fluticasone at 440 microg twice daily resulted in no significant effects on BMD and a statistically significant but not clinically important temporary reduction in cortisol production.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bone Density; Double-Blind Method; Drug Administration Schedule; Drug Monitoring; Eye Diseases; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Time Factors; Treatment Outcome

Patients with severe asthma are often inadequately controlled on existing anti-asthma therapy, constituting an unmet clinical need.. This randomized, double-blind, placebo-controlled trial evaluated the ability of omalizumab, a humanized monoclonal anti-IgE antibody, to improve disease control sufficiently to enable inhaled corticosteroid reduction in patients with severe allergic asthma.. After a run-in period when an optimized fluticasone dose (> or =1000 microg/day) was received for 4 weeks, patients were randomized to receive subcutaneous omalizumab [minimum 0.016 mg/kg/IgE (IU/mL) per 4 weeks; n=126] or matching placebo (n=120) at intervals of 2 or 4 weeks. The study comprised a 16-week add-on phase of treatment followed by a 16-week fluticasone-reduction phase. Short-/long-acting beta(2)-agonists were allowed as needed.. Median reductions in fluticasone dose were significantly greater with omalizumab than placebo: 60% vs. 50% (P=0.003). Some 73.8% and 50.8% of patients, respectively, achieved a > or =50% dose reduction (P=0.001). Fluticasone dose reduction to < or =500 microg/day occurred in 60.3% of omalizumab recipients vs. 45.8% of placebo-treated patients (P=0.026). Through both phases, omalizumab reduced rescue medication requirements, improved asthma symptoms and asthma-related quality of life compared to placebo.. Omalizumab treatment improves asthma control in severely allergic asthmatics, reducing inhaled corticosteroid requirements without worsening of symptom control or increase in rescue medication use.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Humans; Immunoglobulin E; Male; Middle Aged; Omalizumab; Quality of Life; Treatment Outcome

Airway hyperresponsiveness induced by adenosine-5'-monophosphate (AMP) is regarded as a reliable model for allergic asthma and for the evaluation of anti-asthmatic drugs. Single-dose inhaled corticosteroids (ICS) are known to be protective in this model, but the duration of action of these drugs in this model has never been studied. The duration of ICS protection was determined by administration of single-dose fluticasone propionate (FP; 1,000 micrograms) up to 26 h before AMP challenge. A randomised, double-blind, placebo-controlled, four-way crossover study was performed in 13 mild asthmatics (mean +/- SD predicted forced expiratory volume in one second (FEV1) 98 +/- 7%). Each subject received placebo and FP (at 26, 14 or 2 h prior to the AMP challenge). Furthermore, the marker exhaled nitric oxide (eNO) was studied after administration at these time points to investigate whether eNO also demonstrates the duration of action of ICS. The doubling concentrations difference (DCD) of AMP causing a 20% fall in FEV1, when FP was administered 26, 14 or 2 h prior to challenge, was significantly increased as compared with placebo: DCD (95% confidence interval) at 26 h, 0.73 (0.20-1.26), p = 0.008; 14 h, 1.50 (0.99-2.01), p < 0.001; and 2 h, 2.89 (2.37-3.40), p < 0.001. However, eNO was not significantly affected at these time points. In conclusion, a single dose of 1,000 micrograms inhaled fluticasone propionate protects against adenosine-5'-monophosphate airway hyperresponsiveness up to 26 h after dosing. This study suggests that adenosine-5'-monophosphate challenge can be used as a sensitive marker to study the duration of action of inhaled corticosteroids.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Biomarkers; Bronchial Provocation Tests; Bronchoconstriction; Bronchoconstrictor Agents; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Exhalation; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Nitric Oxide; Placebos; Protective Agents; Time Factors

Daily maintenance medications are recommended for all children with mild persistent to severe persistent asthma; however, poor adherence to these medications is common.. To evaluate the impact of school-based provision of inhaled corticosteroids on asthma severity among urban children with mild persistent to severe persistent asthma.. Children aged 3 to 7 years with mild persistent to severe persistent asthma were identified at the start of the 2000-2001 and 2001-2002 school years in Rochester. Children were assigned randomly to a school-based care group (daily inhaled corticosteroids provided through the school) or a usual-care group (inhaled corticosteroids not given through school).. Improvement in parent-reported symptom-free days.. Of 242 eligible children, 184 were enrolled from 54 urban schools. Data for 180 children were available. Parents of children in the school-based care group had a greater improvement in quality of life compared with parents of children in the usual-care group (change score, 0.63 vs 0.24; P =.047); also, children in the school-based care group vs the usual-care group missed less school because of asthma (mean total days missed, 6.8 vs 8.8; P =.047) and experienced more symptom-free days during the early winter months (mean days per 2-week period, 9.2 vs 7.3; P =.02). A post hoc analysis revealed that all significant findings were produced by differences among children who were not exposed to secondhand smoke. Furthermore, among children not exposed to smoke, those in the school-based care group vs the usual-care group had more symptom-free days overall (11.5 vs 10.5; P =.046), had fewer days needing rescue medications (1.6 vs 2.3; P =.03), and were less likely to have had 3 or more acute visits for asthma (6 [13%] of 47 children vs 17 [31%] of 54 children; P =.03).. School-based provision of inhaled corticosteroids significantly improved symptoms, quality of life, and absenteeism among urban children with mild persistent to severe persistent asthma. This effect was seen only among children not exposed to secondhand smoke.

Topics: Absenteeism; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Child, Preschool; Female; Fluticasone; Humans; Male; Multivariate Analysis; New York; Quality of Life; School Health Services; Tobacco Smoke Pollution; Treatment Outcome

Pediatric asthma remains an important public health concern as its prevalence and cost to the health care system is rising. In order to promote innovative research in asthma therapies, the National Heart, Lung and Blood Institute created the Childhood Asthma Research and Education Network in 1999. As its first study, the steering committee of the Childhood Asthma Research and Education Network designed a randomized clinical trial to determine if persistent asthma could be prevented in children at a high risk to develop the disease. This communication presents the design of its first clinical trial, the Prevention of Asthma in Kids (PEAK) trial and the organization of the Childhood Asthma Research and Education Network that developed and implemented this trial. Studies of the natural history of asthma have shown that, in persistent asthma, the initial asthma-like symptoms and loss of lung function occur predominately during the first years of life. Therefore, in the Prevention of Asthma in Kids study, children 2 and 3 years old with a positive asthma predictive index were randomized to twice daily treatment with fluticasone 88 microg or placebo via metered-dose inhaler and Aerochamber for 2 years. The double blind treatment period was followed by a 1-year observational period. Lung function was measured by spirometry and oscillometry technique at 4-month intervals throughout the study. Bronchodilator reversibility and exhaled nitric oxide (ENO) studies were performed at the end of the treatment and observation periods. The primary outcome measure was the number of asthma-free days. Other secondary outcomes included number of exacerbations, use of asthma medications and lung function. These measures were chosen to reflect the progression of the disease from intermittent wheezing to persistent asthma and measurement of the extent of airflow limitation and airway reactivity.

Topics: Administration, Inhalation; Age Factors; Androstadienes; Asthma; Bronchodilator Agents; Child, Preschool; Cohort Studies; Double-Blind Method; Female; Fluticasone; Galvanic Skin Response; Humans; Male; Patient Education as Topic; Patient Selection; Predictive Value of Tests; Preventive Health Services; Prospective Studies; Randomized Controlled Trials as Topic; Respiratory Function Tests; Spirometry

Mometasone furoate (MF) and fluticasone propionate (FP) are high potency inhaled corticosteroids. The systemic bioavailability of MF is claimed to be negligible, leading to a minimal potential for systemic adverse effects. We assessed the overnight urinary cortisol/creatinine as the primary outcome of adrenal suppression in 21 patients with persistent asthma (mean FEV1 = 91%). Patients were randomized in a crossover fashion to receive 2 weekly consecutive doubling incremental doses of either FP Accuhaler (500, 1,000, and 2,000 microg/day) or MF Twisthaler (400, 800, and 1,600 microg/day). For the 21 per protocol completed patients, there was significant suppression of overnight urinary cortisol/creatinine with high and medium doses of both drugs-as geometric mean fold suppression (95% confidence interval) from baseline: FP 2,000 microg, 1.85 (1.21-2.82, p = 0.002); FP 1,000 microg, 1.45 (1.07-1.96, p = 0.02); MF 1,600 microg, 1.92 (1.26-2.93, p = 0.001); and MF 800 microg, 1.39 (1.04-1.88, p = 0.02). For secondary outcomes of 8:00 A.M. plasma cortisol, serum osteocalcin, and early morning urinary cortisol/creatinine, there was significant suppression with MF and FP at the highest dose. Our data refute the assertion that MF has negligible systemic bioavailability and a lower potential for systemic adverse effects compared with FP.

Topics: Administration, Inhalation; Adolescent; Adrenal Glands; Adult; Aged; Androstadienes; Asthma; Biological Availability; Confidence Intervals; Creatinine; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluticasone; Follow-Up Studies; Humans; Hydrocortisone; Male; Middle Aged; Mometasone Furoate; Multivariate Analysis; Pregnadienediols; Probability; Respiratory Function Tests; Severity of Illness Index; Treatment Outcome; Urinalysis

There are no data comparing the relative efficacy of hydrofluoroalkane (HFA) formulations of ciclesonide (CIC) and fluticasone propionate (FP) on airway hyper-responsiveness, in mild-to-moderate persistent asthma. We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP, assessing methacholine challenge, in addition to exhaled nitric oxide, lung function, diary cards and quality of life.. Nineteen mild-to-moderate asthmatic patients completed the study per protocol in randomized, double-blind, double-dummy, crossover fashion. Patients were required to stop their usual inhaled corticosteroid therapy for the duration of the study. Patients were commenced instead on salmeterol (SM) 50 microg one puff twice daily + montelukast (ML) 10 mg once daily for 2-week washout periods prior to each randomized treatment, in order to prevent dropouts. Patients received 4 weeks of either CIC 200 microg two puffs once daily (08.00 h) + CIC-placebo (PL) two puffs once daily (20.00 h) + FP-PL two puffs twice daily (08.00 h and 20.00 h), or FP 125 microg two puffs twice daily (08.00 h and 20.00 h) + CIC-PL two puffs twice daily (08.00 h and 20.00 h). SM + ML were withheld for 72 h prior to post-washout visits and CIC or FP was withheld for 24 h prior to study visits.. There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC20 as doubling dilution (dd) shift from respective baseline; mean difference: 0.4 dd (95% CI -0.4, 1.2). Moreover, there was no difference between treatments for the sequence of CIC first vs FP second; mean difference: 0.2 dd (95% CI -1.3, 1.7) or FP first vs CIC second; mean difference: 0.9 dd (95% CI -0.1, 1.8). There were also no differences for other secondary outcomes between treatments, either respective or irrespective of sequence, as change from baseline.. There were no differences between 4 weeks of CIC 400 microg once daily and FP 250 microg twice daily on methacholine hyper-responsiveness in mild-to-moderate persistent asthma. Longer-term studies are indicated to evaluate their relative efficacy on asthma exacerbations.

Topics: Administration, Inhalation; Androstadienes; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Male; Methacholine Chloride; Middle Aged; Pregnenediones; Vital Capacity

For patients whose asthma is uncontrolled with low-dose inhaled corticosteroids, addition of alternative therapy instead of increasing the steroid dose is recommended by current treatment guidelines.. To compare montelukast, a once-daily leukotriene receptor antagonist, and salmeterol, a twice-daily, long-acting beta-agonist, concomitantly administered with inhaled fluticasone, according to the percentage of patients without an asthma attack for 1 year.. A randomized, double-blind, double-dummy, multicenter study was conducted. Adult patients with moderate-to-severe persistent asthma (ages 14-73 years) receiving inhaled fluticasone (220 microg/d) who remained symptomatic during a 4-week run-in period were randomized to the addition of salmeterol (84 microg/d) or montelukast (10 mg/d) for 48 weeks.. Of the 1,473 randomized patients, 743 were randomized to montelukast and 730 to salmeterol; 1,059 patients completed the study. Eighty percent of patients in the montelukast group and 83.3% of patients in the salmeterol group remained attack free during the 48 weeks of treatment (relative risk, 1.20; 95% confidence interval, 0.96-1.49). Montelukast significantly reduced blood eosinophil counts compared with salmeterol, whereas salmeterol significantly increased prealbuterol forced expiratory volume in 1 second, asthma-specific quality of life, morning peak expiratory flow rate, and decreased nocturnal awakenings compared with montelukast. Differences between treatments were small, and both treatments were generally well tolerated.. Addition of montelukast or salmeterol to an inhaled corticosteroid similarly protected most patients from experiencing an asthma attack during a 1-year period, but, based on noninferiority limits, the study was inconclusive with regard to a difference between treatment groups.

Topics: Acetates; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; History, 16th Century; Humans; Male; Middle Aged; Quinolines; Salmeterol Xinafoate; Sulfides; Treatment Outcome

For most patients, asthma is not controlled as defined by guidelines; whether this is achievable has not been prospectively studied. A 1-year, randomized, stratified, double-blind, parallel-group study of 3,421 patients with uncontrolled asthma compared fluticasone propionate and salmeterol/fluticasone in achieving two rigorous, composite, guideline-based measures of control: totally and well-controlled asthma. Treatment was stepped-up until total control was achieved (or maximum 500 microg corticosteroid twice a day). Significantly more patients in each stratum (previously corticosteroid-free, low- and moderate-dose corticosteroid users) achieved control with salmeterol/fluticasone than fluticasone. Total control was achieved across all strata: 520 (31%) versus 326 (19%) patients after dose escalation (p < 0.001) and 690 (41%) versus 468 (28%) at 1 year for salmeterol/fluticasone and fluticasone, respectively. Asthma became well controlled in 1,071 (63%) versus 846 (50%) after dose escalation (p < 0.001) and 1,204 (71%) versus 988 (59%) at 1 year. Control was achieved more rapidly and at a lower corticosteroid dose with salmeterol/fluticasone versus fluticasone. Across all strata, 68% and 76% of the patients receiving salmeterol/fluticasone and fluticasone, respectively, were on the highest dose at the end of treatment. Exacerbation rates (0.07-0.27 per patient per year) and improvement in health status were significantly better with salmeterol/fluticasone. This study confirms that the goal of guideline-derived asthma control was achieved in a majority of the patients.

Topics: Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Practice Guidelines as Topic; Prospective Studies; Quality of Life; Salmeterol Xinafoate; Surveys and Questionnaires; Time Factors; Treatment Outcome

To compare the efficacy and safety of mometasone furoate dry powder inhaler (DPI) administered once daily in the evening with fluticasone propionate metered-dose inhaler (MDI) administered twice daily.. An 8-week, randomized, open-label, parallel-group study compared mometasone furoate DPI, 400 microg every evening (1 puff daily), with fluticasone propionate MDI, two 125-microg puffs twice daily, in 167 adults and adolescents with moderate persistent asthma previously using fluticasone propionate. The primary efficacy variable was the change in forced expiratory volume in 1 second (FEV1) from baseline to the end point. Variables such as response to therapy and subject satisfaction with the inhaler devices were also analyzed.. Improvement in FEV1 was noted at the week 2 visit with both treatments. This improvement was maintained at the 4- and 8-week visits and at the end point for both groups. The mean percent change in FEV1 from baseline to the end point was 4.58% with mometasone furoate DPI and 6.98% with fluticasone propionate MDI (P = .35). At the end point, physicians rated 62% of the mometasone furoate DPI group as "improved" or "much improved" compared with 47% of the fluticasone propionate MDI group (P = .007). A significantly greater proportion of subjects in the mometasone furoate DPI group "liked the inhaler a lot" vs subjects in the fluticasone propionate MDI group (46.8% vs 22.4%; P = .01). Both treatments were well tolerated.. Mometasone furoate DPI, 400 microg every evening, provided comparable efficacy as fluticasone propionate MDI, two 125-microg puffs twice daily, in subjects with moderate persistent asthma previously treated with fluticasone propionate.

Topics: Adolescent; Adult; Aged; Androstadienes; Asthma; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Mometasone Furoate; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Pregnadienediols

Cytokines which signal via the gamma chain of the interleukin (IL)-2 receptor and the interferons (IFNs) have been shown to enhance T cell survival in vitro by rescuing cells from apoptosis.. A study was undertaken to determine whether treatment with inhaled fluticasone propionate (FP; 250 microg twice daily) for 2 weeks could modulate production of IL-15 or IFN-beta and thereby affect T cell survival in bronchial tissue of 10 patients with mild/moderate asthma. Bronchial biopsy specimens were taken before and on completion of treatment.. The mean (95% CI) number of T cells per unit area decreased in the asthmatic group following 2 weeks of treatment with FP (from 7.0 (5.6 to 8.4) to 4.5 (4.0 to 5.1); p = 0.001). There was an increase in the percentage of T cells undergoing apoptosis following FP treatment as assessed by T cell/TUNEL staining (from 4.5 (2.6 to 6.4) to 8.7 (6.6 to 10.8); p = 0.0001). The percentage of cells staining for IL-15 and IFN-beta in the lamina propria, determined by an alkaline phosphatase biotin streptavidin technique, decreased significantly from baseline values of 31.6 (23.4 to 39.7) to 19.6 (12.5 to 26.7), p = 0.039 for IL-15 and from 18.9 (13.5 to 24.4) to 9.5 (5.9 to 13.1), p = 0.007 for IFN-beta following 2 weeks of treatment with FP. However, only the decrease in the percentage of cells staining for IL-15 was significantly correlated with an increased number of apoptotic T cells following treatment (p = 0.008).. These findings support a novel mechanism for the ability of inhaled corticosteroids to decrease T cell numbers, possibly by downregulation of the cytokine IL-15.

Topics: Administration, Inhalation; Adult; Androstadienes; Apoptosis; Asthma; Biopsy; Bronchi; Bronchodilator Agents; Down-Regulation; Female; Fluticasone; Humans; Interferon-beta; Interleukin-15; Male; T-Lymphocytes

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Asthma; Bronchial Hyperreactivity; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Finland; Fluticasone; Follow-Up Studies; Humans; Male; Middle Aged; Reference Values; Risk Assessment; Severity of Illness Index; Treatment Outcome

Inhaled corticosteroids are currently regarded as the gold standard in anti-inflammatory therapy, however, leukotriene receptor antagonists have been ascribed anti-inflammatory properties.. We directly compared the anti-inflammatory effects of inhaled fluticasone propionate (FP, 100 microg Diskus, twice daily) and oral montelukast (MON 10 mg, nocte) in bronchial biopsies of patients with asthma in a double-blind, double-dummy, parallel-group design.. Bronchial biopsies, serum and urine samples were collected from 36 atopic asthmatics before and after 8 weeks of treatment. Activated T cells (CD25+), eosinophils (MBP+) and mast cells (tryptase+) were analysed by immunohistochemistry. Serum eosinophil cationic protein (ECP) and IL-5 were analysed by radio and enzyme immunoassay (EIA), respectively. Urinary 9alpha-11beta-PGF2 and leukotriene E4 (LTE4) were measured by EIA.. A comparison of changes from baseline [FP/MON ratio (95% confidence interval)] of activated T cells was not different when subjects were treated with FP compared to treatment with MON [1.00 (0.18-4.86); P=0.924]. Following treatment, mast cells in the FP group were significantly lower than in the group treated with MON [0.39 (0.16-0.97); P=0.041]. There was no difference in the number of eosinophils in the lamina propria following either treatment [0.54 (0.05-2.57); P=0.263]. However, treatment with FP resulted in a significantly greater decrease in serum ECP, compared to treatment with MON [0.37 (0.25-0.71); P=0.002].. FP appears to be superior to MON as an anti-inflammatory therapy in mild asthmatics.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Cyclopropanes; Double-Blind Method; Eosinophil Cationic Protein; Female; Fluticasone; Humans; Immunohistochemistry; Interleukin-5; Leukotriene Antagonists; Lung; Male; Mast Cells; Middle Aged; Quinolines; Receptors, Interleukin-2; Sulfides; T-Lymphocytes

To assess long-term effects and side-effects of fluticasone propionate (FP), a 2-yr study was performed, comparing a step-down dose approach (1,000 microg.day(-1), with reductions every 2 months to 500, 200 and 100 microg.day(-1) for the remainder of the study) versus a constant dose (200 microg.day(-1)). In 55 children with chronic persistent asthma, aged 6-10 yrs, airways hyperresponsiveness (AHR) and systemic side-effects (height, bone parameters and adrenal cortical function) were assessed at predetermined intervals in a double-blind prospective 2-yr study. AHR improved after 4 months treatment with 1,000 microg.day(-1) FP followed by 500 microg.day(-1), without significant differences during long-term treatment between the two approaches. Dose-dependent reduction of growth velocity, adrenal cortical function and biochemical bone turnover was found during therapy with 1,000 and 500 microg.day(-1) FP when compared with 200 microg.day(-1). In conclusion, doses of 1,000 and 500 microg.day(-1) fluticasone propionate are associated with marked reductions of growth velocity, bone turnover and adrenal cortical function. However, conventional doses (< or =200 microg.day(-1) fluticasone propionate) appear to be safe in the long-term management of childhood asthma. From a safety point of view, high doses of fluticasone propionate should only be prescribed in exceptions, e.g. in persistent severe asthma.

Topics: Adrenal Cortex; Androstadienes; Asthma; Bone and Bones; Bone Density; Bronchial Hyperreactivity; Bronchodilator Agents; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Growth; Humans; Male; Prospective Studies

The effects of high-dose fluticasone propionate therapy on dynamic cortisol stimulation in severe asthma are unknown.. To evaluate the human corticotropin-releasing factor (hCRF)-stimulated plasma cortisol response to fluticasone propionate therapy in severe asthmatic patients with impaired airway caliber (forced expiratory volume in 1 second [FEV1] < 60% of predicted) and in control subjects.. Ten severe asthmatic patients (mean FEV1, 47% of predicted) and 10 controls (mean FEV1, 104% of predicted) received fluticasone propionate, 2,000 microg/d, via a 750-mL primed spacer for 2 weeks. Plasma cortisol levels before and after hCRF stimulation and overnight 10-hour urinary cortisol excretion corrected for creatinine concentration (OUCC) were measured at baseline after washout and 12 hours after the last dose of fluticasone propionate.. Baseline values before fluticasone propionate use were not significantly different in asthmatic patients vs controls for plasma cortisol before and after hCRF stimulation and OUCC. Comparing values at baseline vs after fluticasone propionate use, there was no significant suppression of plasma cortisol levels before (378.2 vs 357.4 nmol/L) or after (510.5 vs 507.9 nmol/L) hCRF stimulation or OUCC (8.2 vs 7.5 nmoL/mmoL) in asthmatic patients. In controls, all outcomes were significantly suppressed comparing values before vs after fluticasone propionate therapy: plasma cortisol levels before (423.5 vs 200.2 nmol/L; P = .002) and after (503.5 vs 291.1 nmol/L; P = .001) hCRF stimulation and OUCC (6.5 vs 2.4 nmol/mmol; P = .002).. Patients with severe persistent asthma and impaired airway caliber seem to be protected from developing systemic adverse effects with high-dose fluticasone propionate therapy, as evaluated by basal and dynamic measures of hypothalamic-pituitary-adrenal axis activity.

Topics: Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Blood Proteins; Breath Tests; Creatinine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Eosinophil Granule Proteins; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Metered Dose Inhalers; Nitric Oxide; Peak Expiratory Flow Rate; Pituitary-Adrenal System; Ribonucleases; Salmeterol Xinafoate; Theophylline

To determine whether initiation of maintenance treatment with the salmeterol (S)/fluticasone propionate (FP) combination (Seretide/Viani/Advair) is more effective than inhaled steroid alone in patients with asthma symptomatic on short-acting bronchodilator alone.. 150 asthma patients with symptoms and prn use of short-acting bronchodilator at least once a week were randomised to 24 weeks' treatment with either S/FP 50/100 microg bd (n = 78) or FP 100 microg bd (n = 72). The primary endpoint was the percentage of symptom-free 'day + night's.. The percentage of symptom-free 'day + night's increased significantly more for S/FP (20 to 64%) compared to FP (24 to 51%). The treatment difference was 15.3%, P = 0.008. In the sub-group of patients with mild asthma the treatment difference was also statistically significant in favour of S/FP (P = 0.0245, n = 74). S/FP was also significantly superior to FP alone for: lung function, salbutamol use prn, day symptom score, symptom-free days, and episode-free 'day + night's. Treatments were equally well tolerated.. Initial maintenance treatment with S/FP is significantly more effective than with inhaled steroid alone for patients symptomatic when treated with short-acting bronchodilator alone. This also apply to patients with mild persistent asthma.

Topics: Administration, Inhalation; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Steroids; Treatment Outcome

We report a 4 yr follow up study of seven asthmatic children with chronic persistent asthma, high-residual volume and low-density areas at high-resolution computerized tomography after treatment with salmeterol and fluticasone. Improvement of lung function with disappearance of low-density areas in six patients after treatment with fluticasone and montelukast was obtained.

Topics: Acetates; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Fluticasone; Follow-Up Studies; Humans; Lung; Quinolines; Respiratory Function Tests; Salmeterol Xinafoate; Sulfides

Optimal therapy for many patients with persistent asthma requires control of both main components of this disease: inflammation and bronchoconstriction.. To compare the efficacy and safety of initiating maintenance therapy with an inhaled, long-acting beta2-agonist and an inhaled corticosteroid administered from a single device with that of the individual agents alone.. A 12-week, randomized, double-blind study was conducted in patients 12 years and older with persistent asthma who were symptomatic while taking as-needed, short-acting beta2-agonists alone. Treatments were administered twice daily via the Diskus device: salmeterol, 50 microg; fluticasone propionate, 100 microg; or fluticasone propionate, 100 microg, with salmeterol, 50 microg.. Of 555 patients screened, 267 were randomly assigned to treatment. At end point, fluticasone propionate and salmeterol significantly increased predose forced expiratory volume in 1 second (FEV1) compared with salmeterol alone (0.51 +/- 0.05 L vs 0.38 +/- 0.04 L, P = .04). Fluticasone propionate and salmeterol significantly increased area under the serial FEV1 curve at treatment week 12 relative to predose FEV1 (baseline) on treatment day 1 (AUCb1, 8.4 +/- 0.6 L/h; P < or = .02) compared with salmeterol (6.2 +/- 0.5 L/h) and fluticasone propionate (7.0 +/- 0.6 L/h). Fluticasone propionate and salmeterol were significantly (P < or = .02) more effective than the individual agents used alone in improving morning and evening peak expiratory flow rate and asthma symptoms. In addition, fluticasone propionate and salmeterol effectively reduced rescue albuterol use (P < or = .04). All treatments were well tolerated.. In patients symptomatic while taking short-acting beta2-agonists alone, initial maintenance treatment of the 2 main components of asthma, inflammation and smooth muscle dysfunction, with fluticasone propionate and salmeterol, 100 and 50 microg, administered via the Diskus results in greater improvements in overall asthma control compared with treatment of either component alone.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Salmeterol Xinafoate; Treatment Outcome

In a longitudinal ex vivo placebo-controlled study, asthmatics already treated with inhaled corticosteroid received supplemental long-acting beta-agonist (LABA) or increased doses of their inhaled corticosteroid (ICS). Previously reports have shown significant reductions in biopsy eosinophil numbers after treatment with LABA. Following these findings, eosinophil chemokines eotaxin and IL-5 in the BAL fluid at baseline and after 3 months of study medication have now been measured, and these data with that from new cross-sectional controls have also been compared. It is hypothesised that changes in airway eosinophils would be related to eosinophil cytokines.. BAL cytokines were measured by chemiluminescent enzyme-linked immunosorbent assay, while eosinophils were measured by immunohistochemistry or differential cell counting. For all measures, longitudinal data were compared to that from ICS-free asthmatics (n = 42) and non-asthmatic controls (n = 28).. BAL eotaxin in asthmatics was elevated above non-asthmatic levels regardless of ICS levels. BAL IL-5 was elevated in ICS-free asthmatics, but not in asthmatics on low-dose ICS treatment. Longitudinally, BAL eotaxin was unchanged after 3 months. Unexpectedly, IL-5 increased after 3 months of additional LABA treatment but was not further affected by increasing the dose of ICS. Airway eotaxin seemed to be constitutively raised in asthmatics, whereas, IL-5 levels were more steroid-responsive. No relationship was observed between eosinophils and eosinophilic cytokines in the BAL.. While the elevation of luminal IL-5 with LABA treatment cannot be accounted for, it may have contributed to luminal clearance of airway wall eosinophils. The lack of correlation between airways eosinophils and eosinophilic cytokines in the BAL is particularly important.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Chemokine CCL11; Chemokines, CC; Cross-Sectional Studies; Fluticasone; Humans; Interleukin-5; Longitudinal Studies; Salmeterol Xinafoate; Treatment Outcome

We evaluated whether montelukast conferred additive effects in patients with asthma receiving fluticasone/salmeterol (FP/SM) combination and FP alone. Twenty-two patients with mild to moderate asthma completed a double-blind, placebo-controlled study. After a 2-week run-in using FP 250 microg/SM 50 microg 1 puff twice daily, patients entered a randomized crossover period to receive additional montelukast 10 mg daily or placebo for 3 weeks each. For the first 2 weeks, they received FP/SM 1 puff BID, and then they received FP 250 microg 1 puff BID for the 3rd week. The primary outcome was adenosine monophosphate challenge threshold and recovery time; secondary outcomes included surrogate inflammatory markers and lung function. Compared with FP/SM run-in, adding montelukast to FP/SM was better (p < 0.05) than placebo for inflammatory markers but not for lung function. For adenosine monophosphate threshold, recovery, exhaled nitric oxide, and blood eosinophils, there were 1.4 (95% confidence interval, 1.1-1.8) geometric mean fold, 10 minutes (3-17 minutes), 2.1 parts per billion (0.2-3.9 parts per billion), and 88 (34-172) x 10(6)/L differences, respectively. The combination of FP plus montelukast was superior to FP/SM for inflammatory markers but was inferior for lung function. Thus, in patients taking FP/SM or FP, montelukast conferred complimentary effects on surrogate inflammatory markers, which were dissociated from lung function. Further studies are required to evaluate whether these effects of montelukast translate into clinical benefits.

Topics: Acetates; Adenosine Monophosphate; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Biomarkers; Bronchial Provocation Tests; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Salmeterol Xinafoate; Severity of Illness Index; Sulfides; Treatment Outcome

We conducted a randomized, double-blind, parallel-group study to assess the effect of 6 weeks treatment with low-dose (100 microg twice a day) or high-dose (500 microg twice a day) inhaled fluticasone propionate (FP) on the vascular component of airway remodeling in 30 patients with mild to moderate asthma. We also studied the effect on the inflammatory cells and the basement membrane thickness, and we compared findings from bronchial biopsies taken in patients with asthma with those in eight control subjects. Bronchial responsiveness to methacholine and asthma symptom score were measured before and after treatments. Eight patients in the low-dose FP group and eight patients in high-dose FP group completed the study. At baseline, patients with asthma showed an increase in the number of vessels and in vascular area as compared with control subjects. In the subjects with asthma, number of vessels correlated with vascular area (p < 0.01) and with number of mast cells (p < 0.01). Bronchial responsiveness to methacholine, asthma symptom score, and inflammatory cells decreased significantly after both low- and high-dose FP (p < 0.05). However, the number of vessels, the vascular area, and the basement membrane thickness decreased only after high-dose FP (p < 0.05). In conclusion, this study shows that in patients with mild to moderate asthma, high dose of inhaled FP given over 6 weeks can significantly affect airway remodeling by reducing both submucosal vascularity and basement membrane thickness.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Basement Membrane; Biopsy; Bronchi; Bronchoconstrictor Agents; Bronchodilator Agents; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Inflammation; Male; Methacholine Chloride; Time Factors

The aim of the study was to investigate the effect of addition of montelukast to inhaled fluticasone propionate (FP) therapy, compared with FP therapy alone (100 microg twice a day) on airway immunopathology in individuals with mild asthma. Twenty-eight subjects received FP (100 microg twice a day) or FP (100 microg twice a day) plus montelukast (10 mg at night) for 8 weeks and were then crossed over to the alternate treatment for a further 8 weeks. Physiological measurements and bronchial biopsies were obtained at +/- 2 days before treatment and +/- 2 days at the end of each treatment period. A two-period crossover analysis was performed and the mean and SE were calculated. There was no significant difference in percent predicted FEV1 (p = 0.51) or PC20 mg/ml (p = 0.81) between the two treatment regimes after 8 weeks of therapy. There was no difference in the efficacy of either treatment in decreasing T cell (p = 0.97), CD45RO+ (p = 0.37), mast cell (p = 0.37), or activated eosinophils (p = 0.55) numbers in bronchial biopsies. There was no significant difference in the percentage area stained for IFN-gamma (p = 0.76) or interleukin-4 (p = 0.61) between treatments. Reduction of inflammatory cell numbers in the bronchial mucosa achieved with FP plus montelukast was not significantly different from the reduction observed with FP alone in individuals with mild asthma.

Topics: Acetates; Administration, Inhalation; Administration, Topical; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Biopsy; Bronchi; Bronchodilator Agents; Cross-Over Studies; Cyclopropanes; Data Interpretation, Statistical; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Immunohistochemistry; Inflammation; Interferon-gamma; Interleukin-4; Leukotriene Antagonists; Male; Middle Aged; Placebos; Quinolines; Sulfides; Time Factors

The use of nebulization for the administration of inhaled steroids plays an important role in asthma patients who are unable to use pressurized aerosol or dry-powder inhalers effectively. Moreover, the type of nebulizer used may affect how much drug is delivered to the lungs. The objective of this multinational, multicentre, randomized, active-controlled, parallel-group study was to compare the efficacy and safety of nebulized corticosteroids in adult patients with chronic asthma. Following a 1-week placebo run-in period, 205 patients, aged 18-65 years, with moderate persistent asthma were randomized to one of two treatment groups for 12 weeks: beclometasone dipropionate (BDP) suspension for nebulization 2,400 microg day(-1) b.i.d. (n = 103), or fluticasone propionate (FP) suspension for nebulization 2,000 microg day(-1) b.i.d. (n = 102), both administered by a jet nebulizer Comparable efficacy in controlling asthma was demonstrated by the two treatments at study end, as evident when evaluating various efficacy parameters (pulmonary function tests, asthma exacerbations and symptoms, and the use of rescue salbutamol). The primary efficacy endpoint was the variation in the pulmonary expiratory flow (PEF) at treatment end over the baseline visit. For the intent-to-treat population, in the BDP group mean PEF values increased statistically significantly from 5.2 +/- 1.31 s(-1) to 5.7 +/- 1.61 s(-1), while in the FP group the increase was from 5.2 +/- 1.21 s(-1) to 5.8 +/- 1.81 s(-1). Mean PEF values as per cent of predicted also increased in a statistically significant way, from 71% to 77.1 % in the BDP group, and from 70.1% to 76.9% in the FP group. The two treatments were equally well tolerated.A total of 23 and 32 patients in the BDP and FP groups, respectively, reported adverse events during the treatment period, and these were generally mild. In conclusion, the results of this study demonstrate that BDP 2,400 microg day(-1) and FP 2,000 microg day(-1), both suspensions for nebulization administered via a jet nebulizer, are equally effective, with an acceptable safety and tolerability profile, when used in adult patients with moderate persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chronic Disease; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Vital Capacity

All currently available inhaled corticosteroids reach the systemic circulation and have the potential to produce adverse effects with long term use. This risk is often assessed by measuring the effect of different inhaled corticosteroids on the hypothalamic-pituitary-adrenal (HPA) axis in healthy subjects. Absorption of fluticasone propionate and its effects on the HPA axis are greater in healthy subjects than in subjects with moderately severe asthma, but we have failed to show any difference in morning budesonide plasma levels or systemic effects between healthy and asthmatic subjects following inhalation of budesonide. To provide more information on the absorption of fluticasone propionate and budesonide, we have compared the plasma levels of both drugs over 8 hours in healthy and asthmatic subjects.. The area under the plasma concentration-time curves (AUC) and the maximum concentration (Cmax) of fluticasone propionate and budesonide after a single inhaled dose of each drug were compared in 12 healthy control subjects and 12 subjects with moderately severe asthma.. Peak plasma levels of budesonide occurred much earlier and were approximately 20-fold higher than those of fluticasone propionate in both healthy and asthmatic subjects. The AUC and Cmax for fluticasone propionate were lower by 307 (95% CI 62 to 522) pg/ml/h or 43% (p=0.02) and 52 (95% CI -11 to 115) pg/ml or 39% (p=0.1) in subjects with asthma compared with healthy control subjects. In contrast, the AUC and Cmax for budesonide were almost identical between the two groups (mean differences 826 (95% CI -1493 to 3143) pg/ml/h (p=0.5) and 157 (95% CI -1026 to 1339) pg/ml (p=0.8).. Following inhalation, healthy subjects have higher plasma levels of fluticasone propionate than subjects with asthma whereas budesonide plasma levels are similar in the two groups of subjects. Comparing the systemic effects of budesonide and fluticasone propionate in healthy subjects is unlikely to be relevant to subjects with asthma.

Topics: Administration, Inhalation; Androstadienes; Area Under Curve; Asthma; Bronchodilator Agents; Budesonide; Case-Control Studies; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Powders

The aim of this study was to compare the efficacy and safety of salmeterol/fluticasone propionate combination product (SFC) with fluticasone propionate (FP) plus oral montelukast (M) over 12 weeks in symptomatic asthma patients. The study was a multinational, randomised, double-blind, double-dummy, parallel-group design in patients aged > or = 15 years. After a 4-week run-in during which all patients received FP 100 microg twice daily, patients were randomised to inhaled SFC (50/100 microg) twice daily or inhaled FP 100 microg twice daily and oral M 10 mg once daily. Patients kept daily records of their peak expiratory flow (PEF) symptom scores and use of rescue medication. Over the 12-week treatment period, the adjusted increase in mean morning PEF was significantly greater in the SFC group (36 l/min) than the FP/M group (19 l/min; P < 0.001). The improvement in FEV1 was also significantly greater in the SFC group (mean treatment difference 0.11 l; P < 0.001). SFC provided significantly better control of daytime and night-time symptoms and there were fewer exacerbations. Patients in the SFC group were also significantly more likely to have a rescue-free day. Both treatments were equally well tolerated. Combination therapy with FP plus salmeterol (SFC) produced significantly greater improvements in lung function and asthma control than the addition of montelukastto FP.

Topics: Acetates; Administration, Oral; Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Quinolines; Salmeterol Xinafoate; Sulfides; Treatment Outcome

Secondary to phasing out chlorofluorocarbons (CFCs), the fluticasone propionate (FP) pressurized metered-dose inhaler has been formulated in a nonozone-depleting propellant, hydrofluoralkane (HFA) 134a.. To demonstrate equivalent efficacy and safety of FP 200 microg daily propelled by HFA 134a to FP 200 microg daily propelled by CFCs 11 and 12 over a four-week treatment period in pediatric asthmatic patients.. The study was multinational, randomized, double blind and of parallel group design. Eligible patients aged 16 years and younger were steroid naive or receiving 500 microg/day or less of beclomethasone dipropionate, budesonide or flunisolide, or 250 microg/day or less of inhaled FP. The primary efficacy variable was mean morning peak expiratory flow with equivalence determined if the 90% CIs for the treatment differences between groups were within +/- 15 L/min.. Three hundred fifteen patients (mean age 9.3 +/- 2.8 years) were randomly assigned; 158 patients received FP HFA 134a and 157 patients received FP CFC. Over the four-week treatment period, mean morning peak expiratory flow increased from baseline in both groups (14 L/min and 17 L/min, respectively), with a mean treatment difference of -2 L/min. Equivalence was demonstrated between the groups (90% CI -6 to +3 L/min; P=0.589). Both formulations were well tolerated with no serious drug-related events.. FP propelled by HFA 134a has equivalent efficacy and comparable safety to FP propelled by CFC propellants at a microgram equivalent dose in pediatric asthmatic patients.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Asthma; Child; Child, Preschool; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Follow-Up Studies; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Male; Nebulizers and Vaporizers; Probability; Respiratory Function Tests; Severity of Illness Index; Treatment Outcome

Twenty-seven subjects with moderate asthma at the time of diagnosis, well controlled under regular fluticasone propionate (FP) (250 microg b.i.d.) for 6 months at least, were randomized to receive in double-blind fashion: FP 125 microg b.i.d. (Group 1) or FP 50 microg b.i.d. (Group 2) or placebo (Group 3) for 3 months or until symptom recurrence. Daily symptom score and peak expiratory flow were monitored. At the beginning and at the end of the study subjects underwent methacholine challenge and sputum induction. Recurrence of symptoms occurred shortly after randomization in all subjects receiving placebo. None from Group 1 or 2 experienced symptom recurrence during the study. No significant difference in clinical and functional data, and in sputum eosinophil percentages was observed between the beginning and the end of the study in both Groups 1 and 2. Subjects from Group 3 showed a significant increase of sputum eosinophils (P<0.05) and a significant decrease in provocative dose of methacholine (P<0.05) when asthma symptoms recurred. Therefore, very low doses of FP (50 microg b.i.d.) are effective in maintaining for 3 months a good control of the disease in asthmatics already stable under high-dose fluticasone, considering both clinical and functional outcomes and markers of airway inflammation.

Topics: Adult; Androstadienes; Asthma; Bronchoconstrictor Agents; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Methacholine Chloride; Middle Aged; Recurrence; Sputum

This study was designed to determine whether the benefit of adding salmeterol was superior to doubling the dose of fluticasone propionate (FP) over 6 months, compared to a control group who remained on a lower dose of FP. The multi-centre, double-blind, parallel group study involved 496 symptomatic asthmatic patients with a history of exacerbations on 500-800 micrograms (microg) inhaled corticosteroids (ICS) twice daily (b.d.) in a broadly representative group of 100 hospitals and general practices in six countries. Two doses of FP--250 microg b.d. (FP250) or 500 microg b.d. (FP500)--were compared with the lower dose of FP plus a long-acting beta2-agonist, salmeterol 50 microg b.d. (SM/FP250). Patients symptomatic on the run-in dose of FP250 alone formed the control group in the treatment period. Over 6 months, SM/FP250 significantly improved mean morning peak expiratory flow rates (amPEF) by 42.1 l/min, more than twice the improvement achieved with either dose of FP alone. SM/FP250 also resulted in more symptom-free days and nights (P < 0.002) and days and nights with no relief medication (P < 0.001). The number of severe exacerbations was low: 3, 6 and 8% in the SM/FP250, low- and high-dose FP groups, respectively. This study confirms that adding salmeterol to low-dose inhaled FP offers greater improvements than either maintaining or doubling the dose of FP. Significant benefit was gained from adding salmeterol in a group of patients who appeared to have been at the top of their steroid dose-response curve receiving FP250. There was no evidence of tolerance and a low incidence of exacerbations in all treatment groups.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Treatment Outcome

Current guidelines advocate adding a long acting beta(2)-agonist (LABA) to an inhaled corticosteroid as an alternative to increasing the dose of the latter. Since it is unclear how this translates into effects on surrogate inflammatory markers, we evaluated the anti-inflammatory activity of fluticasone plus salmeterol in combination versus twice the dose of fluticasone alone.. Fifteen mild-to-moderate asthmatics (mean FEV(1) 80% predicted) uncontrolled on inhaled corticosteroids (mean dose 470 microg) were randomised in a single-blind crossover fashion to receive 2 weeks each of fluticasone 250 microg plus salmeterol 50 microg in combination (FP+SM), 1 puff b.i.d., and fluticasone 500 microg (FP), 1 puff b.i.d. Prior to each randomised treatment, there was a 2-week run-in and washout period during which patients used their usual inhaled corticosteroid therapy. Measurements were made before and after randomised treatment periods. The primary outcome was airway hyper-responsiveness to adenosine monophosphate (AMP PC(20)), while secondary endpoints were exhaled tidal nitric oxide (NO), forced expiratory volume in 1 second (FEV(1)) and forced mid-expiratory flow (FEF(25-75)).. For AMP PC(20), FP alone but not FP+SM conferred a significant ( P<0.05) improvement amounting to 3.27 (95% CI 1.46-7.32) and 1.44 (95% CI 0.64-3.23) geometric mean fold shifts, respectively, from baseline, while the difference between treatments was significantly ( P<0.05) greater with FP alone: a 2.26-fold (95% CI 1.01-5.07) difference. Both FP alone and FP+SM conferred significant ( P<0.05) falls in NO from baseline: 2.33 (95% CI 1.71-3.19) and 1.49 (95% CI 1.09-2.03) geometric mean fold changes, respectively, while between treatments the reduction was significantly ( P<0.05) greater with FP alone: a 1.57-fold (95% CI 1.15-2.14) difference. Neither treatment significantly improved FEV(1) or FEF(25-75).. Double the dose of FP alone relative to FP+SM conferred superior effects on surrogate inflammatory markers but not on lung function. Long-term studies are required to evaluate whether these improvements on surrogate inflammatory markers translate into commensurate reductions in airway remodelling and exacerbations.

Topics: Adenosine Monophosphate; Adult; Albuterol; Androstadienes; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Bronchodilator Agents; Cross-Over Studies; Drug Therapy, Combination; Endpoint Determination; Fluticasone; Humans; Respiratory Function Tests; Salmeterol Xinafoate; Single-Blind Method

Few dose ranging studies have investigated optimal dosing with inhaled corticosteroids in children with asthma.. To compare the efficacy and tolerability of fluticasone propionate 100 or 200 microg twice daily in children with moderate to severe asthma for one year.. One year, randomised, double blind, parallel group, multicentre study. Children aged 4-11 years (n = 528) with moderate to severe asthma who had previously received high dose inhaled corticosteroids were given fluticasone propionate 100 or 200 microg twice daily for the 52 week treatment period. Efficacy (exacerbations, lung function, and symptoms) and tolerability (adverse events and cortisol levels) were measured.. There was a non-significant decreased risk of experiencing an exacerbation at any time with fluticasone propionate 200 microg twice daily compared with fluticasone propionate 100 microg twice daily. This difference reached significance among patients with more severe asthma (defined by previous inhaled corticosteroid dose >800 microg/day). Daily record card morning peak expiratory flow (PEF) in the total population improved significantly more with the higher dose of fluticasone propionate (between group difference, weeks 1-52: 11.4 l/min). Clinic visit mean PEF improved from baseline with both doses, but the response was significantly greater with the higher dose (between group difference, week 52: 17.8 l/min). Both doses were equally well tolerated and overnight urinary cortisol concentrations were unchanged or slightly increased during treatment with either dose.. This long term dose comparison study shows that treatment with fluticasone propionate 200 micro g twice daily may offer benefits over a lower dose, particularly in children with more severe asthma.

Topics: Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Hydrocortisone; Male; Peak Expiratory Flow Rate

Unmeasured confounders and selection bias can significantly influence the results of retrospective observational analyses of asthma therapy.. To evaluate the efficacy of oral montelukast and inhaled fluticasone propionate in a randomized, prospective 12-month "real-world" observational analysis of children with mild persistent asthma.. Children (n = 104) between 6 and 15 years of age with mild asthma as determined by forced expiratory volume in 1 second, symptoms, and evaluation by an experienced pediatric allergist or pulmonologist, who were not currently receiving controller therapy, were randomly assigned to fluticasone or montelukast on an alternating basis. Subjects were asked to complete a questionnaire at 6 and 12 months; otherwise, medical care was identical to that of similar managed care patients. Outcome parameters were evaluated after 12 months by claims database analysis. An acute asthma attack requiring emergent care was the primary outcome parameter. Measures of adherence, symptoms, and asthma control, as measured by the pediatric Asthma Therapy Assessment Questionnaire, were secondary outcome parameters.. Demographics, spirometry, symptoms at enrollment, emergent care visits, asthma hospitalizations, routine office visits, and symptoms at study completion were not significantly different between study groups. Adherence, as evaluated by the number of controller fills, was significantly (P = 0.0003) better for montelukast (7.65 +/- 3.01) than fluticasone (5.46 +/- 3.01). Similar numbers of subjects in each study group required beta-agonists and oral prednisone.. These results suggest that oral montelukast and inhaled fluticasone have similar real-world efficacies in the treatment of children with mild asthma, possibly as a result of the significantly better adherence with oral montelukast therapy compared with inhaled fluticasone.

Topics: Acetates; Administration, Intranasal; Administration, Oral; Adolescent; Adrenergic beta-Agonists; Androstadienes; Anti-Bacterial Agents; Asthma; Bronchodilator Agents; Child; Cyclopropanes; Emergency Medical Services; Female; Fluticasone; Humans; Leukotriene Antagonists; Male; Patient Compliance; Peak Expiratory Flow Rate; Pilot Projects; Prednisolone; Prospective Studies; Quinolines; Sulfides

Bronchial hyperresponsiveness (BHR) is characteristic of asthmatic airways, is induced by airway inflammation, and is reduced by inhaled corticosteroids (ICS). The time course for the onset and cessation of the effect of ICS on BHR is unclear. The effect of inhaled fluticasone propionate (FP) on BHR in patients with mild persistent asthma was assessed using time intervals of hours, days and weeks.. Twenty six asthmatic patients aged 21-59 years were selected for this randomised, double blind, parallel group study. The effect of 250 micro g inhaled FP (MDI) administered twice daily was compared with that of placebo on BHR assessed using a dosimetric histamine challenge method. The dose of histamine inducing a decrease in forced expiratory volume in 1 second (FEV(1)) by 15% (PD(15)FEV(1)) was measured before and 6, 12, 24 and 72 hours, and 2, 4 and 6 weeks after starting treatment, and 48 hours, 1 week and 2 weeks after cessation of treatment. Doubling doses of changes in PD(15)FEV(1) were calculated and area under the curve (AUC) statistics were used to summarise the information from individual response curves.. The increase in PD(15)FEV(1) from baseline was greater in the FP group than in the placebo group; the difference achieved significance within 72 hours and remained significant until the end of treatment. In the FP group PD(15)FEV(1) was 1.85-2.07 doubling doses above baseline between 72 hours and 6 weeks after starting treatment. BHR increased significantly within 2 weeks after cessation of FP treatment.. A sustained reduction in BHR to histamine in patients with mild asthma was achieved within 3 days of starting treatment with FP at a daily dose of 500 micro g. The effect tapered within 2 weeks of cessation of treatment.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Treatment Outcome

Inhaled corticosteroids are recommended as first-line therapy for pediatric asthma. However, few controlled long-term studies have investigated their effect on bone mineral density (BMD) and growth.. Children who were aged 6 to 14 years and had persistent asthma were randomized to 24 months' treatment with fluticasone propionate (FP) 200 micro g/d or nedocromil sodium (NS) 8 mg/d (if uncontrolled, maximum doses of 400 micro g/d and 16 mg/d, respectively). BMD was assessed blind and analyzed at a central facility on the basis of dual-energy x-ray absorptiometry measurements of the lumbar spine and femoral neck at months 0, 6, 12, and 24. Height was measured at months 0, 12, and 24. Efficacy parameters (lung function, asthma control, occurrence of exacerbations) were measured every 3 months.. In total, 174 children were randomized to treatment (87 received FP, and 87 received NS). At month 24, the adjusted mean percentage increase in lumbar spine BMD was 11.6% in the FP group compared with 10.4% in NS-treated children (95% confidence interval for treatment difference: -0.7% to 3.1%). The corresponding increases in femoral neck BMD were 8.9% and 8.5%, respectively. There was no significant difference in growth between the 2 groups: adjusted mean growth rates were 6.1 cm/y with FP and 5.8 cm/y with NS. FP was significantly superior for every efficacy parameter investigated and was similarly well tolerated as NS.. The long-term effects of FP and NS on BMD accrual and growth are similar among children with asthma. The benefit:risk ratio of FP may be considered superior to that of NS.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Body Height; Bone and Bones; Bone Density; Child; Child Development; Female; Fluticasone; Humans; Longitudinal Studies; Lumbar Vertebrae; Male; Nedocromil; Peak Expiratory Flow Rate; Sex Characteristics; Treatment Outcome

The vasoconstrictive efficacies of glucocorticosteroids (GS) are usually compared by the McKenzie skin-blanching test and taken as an index of relative potency. The rationale for the present study was to transpose the McKenzie test to the airway and to compare the airway vascular effects of three inhaled GS: beclomethasone dipropionate (BDP), fluticasone propionate (FP) and budesonide (BUD), in healthy subjects and patients with mild stable asthma. A soluble, inert gas-uptake method was used to measure airway blood flow (Qaw). Baseline mean+/-SD Qaw normalised for anatomical dead space was 53.1+/-1.4 microL x min(-1) x mL(-1) in healthy subjects (n=10) and 67.8+/-3 microL x min(-1) x mL(-1) in asthmatics (n=10). All GS caused a transient decrease in Qaw. The magnitude of the vasoconstriction was greater in asthmatics. The relative vasoconstrictive effect of BDP, FP and BUD was 1, 1.9, and 2.7, respectively, in asthmatics and 1, 3.3 and 3.0, respectively, in healthy subjects, as assessed by the dose required to decrease Qaw by 20%, from the baseline, 30-min postdrug inhalation. Therefore, measuring airway blood flow may be a useful, site-specific parameter to assess the tissue bioavailability and vasoconstrictive efficacy of inhaled glucocorticosteroids.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; Budesonide; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; Male; Middle Aged; Reference Values; Regional Blood Flow; Severity of Illness Index; Vasoconstriction

Inhaled steroids are the most commonly used anti-inflammatory agents for asthma and are increasingly recognised as having a more rapid onset of action than was previously thought. We have investigated the effect of a single dose of inhaled steroid on nocturnal worsening of asthma.. Ten patients with steroid naive moderate asthma and nocturnal asthma participated in a randomised, double blind, placebo controlled, crossover trial. Participants spent three nights in the laboratory, one week apart. On each night they underwent spirometric testing at 16.00 hours and received one of the three treatments (placebo, beclomethasone 1000 micro g, or fluticasone 1000 micro g) delivered by metered dose inhaler. Spirometric tests were repeated at 04.00 hours the following morning.. Following placebo administration the mean (SE) overnight fall in FEV(1) was 0.65 (0.27) l compared with -0.02 (0.13) l following fluticasone (p=0.019) and 0.23 (0.12) l following beclomethasone (p=0.048 v placebo).. A single dose of inhaled steroid (within the therapeutic range) reduced the fall in FEV(1) in patients with nocturnal asthma when administered at 16.00 hours. Nocturnal worsening of asthma is a useful model for testing inhaled steroid activity in a single night study.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged

Inhaled steroids such as fluticasone propionate and beclomethasone dipropionate play a central role in the treatment of bronchial asthma. Fluticasone exhibits excellent clinical effectiveness; however, oral adverse effects can occur.. To compare the frequency of oral candidiasis in asthmatic patients treated with fluticasone and beclomethasone, to evaluate the effect of gargling with amphotericin B, and to measure the inhalation flow rate on candidiasis.. The study consisted of 143 asthmatic patients who were treated with inhaled steroids, 11 asthmatic patients not treated with inhaled steroids, and 86 healthy volunteers. Quantitative fungal culture was performed by aseptically obtaining a retropharyngeal wall swab from these patients. Patients with positive results were treated with gargling using a 1:50 dilution amphotericin B solution. In asthmatic patients treated with fluticasone, the inhalation flow rate was measured using an inspiratory flow meter.. The amount of Candida spp. was significantly greater in asthmatic patients taking inhaled steroids compared with those who were not. It was also significantly greater in patients with oral symptoms than asymptomatic patients and significantly greater in asthmatic patients treated with fluticasone than in those treated with beclomethasone. Although the presence of Candida did not correlate with the inhaled dose of beclomethasone, it did increase with the dose of fluticasone. Gargling with amphotericin B was effective in most asthmatic patients with candidiasis. Candidiasis was not due to inappropriate flow rates during inhalation of steroids.. Fungal culture of a retropharyngeal wall swab may be useful for predicting the risk of developing oral candidiasis in asthmatic patients treated with inhaled steroids. The amount of isolated Candida was significantly greater in asthmatic patients treated with fluticasone than in those treated with beclomethasone. Attention to dosage is required as the amount of Candida increased with dose of fluticasone. Gargling with a 1:50 dilution of amphotericin B is effective in treating oral candidiasis of asthmatic patients treated with inhaled steroids.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Amphotericin B; Androstadienes; Anti-Inflammatory Agents; Antifungal Agents; Asthma; Beclomethasone; Candidiasis, Oral; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Fluticasone; Glucocorticoids; Humans; Japan; Male; Middle Aged; Regression Analysis; Statistics as Topic; Treatment Failure

Salmeterol (SLM) is a long-acting beta(2)-receptor agonist that produces bronchodilatation for 12 hours in asthmatic subjects. The effects of the regular use of long-acting beta(2)-agonists on airway inflammation are largely unknown.. We examined the effects of 16 weeks of treatment with 50 microg SLM bid, 250 microg fluticasone propionate (FP) bid,5 mg disodium cromoglycate (DSCG) qid, or placebo on airway inflammation in bronchial mucosa.. Airway inflammation was assessed in bronchial biopsy specimens before and after treatments and bronchial hyperresponsiveness (BHR) in 80 patients with newly diagnosed asthma. Inflammatory cells and tenascin in the basement membrane were studied with immunohistochemical methods. Peak expiratory flow rate (PEF), symptoms, and need for rescue medication were recorded.. SLM, FP, and DSCG reduced symptoms and need for rescue medication (P <.04). Both SLM and FP improved PEF and increased PD15FEV(1) to histamine by 2.8 and 5.2 doubling dose units, respectively. Both compounds reduced BHR more than placebo (P <.05). Both SLM and placebo had no effect on any inflammatory cell type. In both FP-treated and DSCG-treated patients, the number of EG2-positive eosinophils in the airway mucosa decreased (P =.002 and P <.05, respectively).. SLM showed no anti-eosinophil properties in this study, but it provided good symptom control. FP provided the best anti-eosinophil properties and symptom relief of the studied compounds.

Topics: Adult; Airway Obstruction; Albuterol; Androstadienes; Asthma; Biopsy; Bronchi; Cromolyn Sodium; Double-Blind Method; Eosinophils; Female; Fluticasone; Humans; Lung; Male; Middle Aged; Salmeterol Xinafoate

The clinical benefit of combining long-acting beta(2)-agonists with inhaled corticosteroids rather than doubling the dose of corticosteroid has been well-documented. However, there are concerns that this might result in a masking of underlying airway inflammation.. The aim of this study was to test the hypothesis that the addition of the long-acting beta(2)-agonist salmeterol (SALM) to a low dose of the inhaled corticosteroid fluticasone propionate (FP) has a steroid-sparing effect and does not result in a worsening of bronchial inflammation compared to doubling the dose of inhaled corticosteroid.. Fifty-six asthmatic subjects, previously not well-controlled on inhaled corticosteroids, were randomized to receive 3 months of treatment with inhaled FP 500 microg twice a day (FP 1000) or FP 200 microg twice a day plus SALM 50 microg twice a day (FP 400 + SALM). Fluticasone propionate 200 microg twice a day served as the control (FP400). Bronchial mucosal biopsy specimens, bronchial washings (BW), and bronchoalveolar lavage were obtained before and after treatment. The primary end points for the study were submucosal mast cell and eosinophil counts.. There was a significant improvement in FEV(1) in the FP400 + SALM group compared to both the FP400 and FP1000 groups. This was accompanied by a significant improvement in peak expiratory flow in the FP400 + SALM group in both the morning and evening compared to the FP1000 group. There were no significant between treatment differences in the change in the number of submucosal mast cells or eosinophils. However, in the FP400 + SALM group there was a significant decrease in submucosal mast cells after 12 weeks of treatment. The addition of SALM to FP was not associated with any increases in airway inflammation in the biopsy specimens, bronchoalveolar lavage, or bronchial washings.. These findings confirm that addition of SALM to FP has clinical benefits but does not mask or exacerbate airway inflammation and suggest that long-acting beta(2)-adrenoceptor agonists might influence mast cell numbers.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Asthma; Biopsy; Bronchi; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Inflammation; Lung; Male; Middle Aged; Salmeterol Xinafoate

Topics: Albuterol; Androstadienes; Asthma; Cross-Over Studies; Drug Therapy, Combination; Fluticasone; Humans; Inflammation; Lung; Muscle, Smooth; Salmeterol Xinafoate

Inhaled corticosteroids alone or in combination with long acting beta2-agonists are indicated for use in mild persistent asthmatics. We set out to evaluate effects on airway hyperresponsiveness (AHR) and airway calibre using hydrofluoroalkane fluticasone/salmeterol (FP/SM) vs. double the dose of fluticasone alone (FP).. Fourteen mild persistent asthmatics completed a randomized double-blind crossover study with 1-week run-in and washout periods prior to treatments. Subjects received 3 weeks of FP 250 microg or FP 125 microg/SM 25 microg as 1 puff twice daily. Methacholine PD20 and lung function were measured after both baseline and treatment periods.. There were no significant differences in baseline values prior to randomized treatments. Compared with pooled baseline, FP/SM and FP conferred improvements (P < 0.05) on methacholine PD20: 2.5 (95% confidence interval 1.7, 3.2) and 1.6 (0.8-2.3) doubling dose improvements, respectively; between FP/SM vs. FP there was a 0.9 (0.4, 1.4) doubling dose difference (P < 0.05). For forced expiratory volume in 1 s (FEV1), forced mid-expiratory flow (FEF25-75) and morning peak expiratory flow (PEF), FP/SM but not FP conferred improvements (P < 0.05) compared with pooled baseline, with FP/SM being greater than FP (P < 0.05): differences in FEV1 of 7.2% (3.8, 10.6) predicted, FEF25-75 of 11.2% (6.3, 16.1) predicted, and morning PEF of 17 L x min(-1)(1-32).. FP/SM conferred improvements on AHR and airway calibre, while twice the dose of FP improved only AHR in patients with mild asthma. The differential effects of FP/SM and FP suggest separate but complementary actions of the two moieties on airway inflammation and smooth muscle stabilization. This may explain the beneficial effects of combination inhalers on exacerbations.

Topics: Adult; Albuterol; Androstadienes; Asthma; Bronchi; Bronchoconstrictor Agents; Bronchodilator Agents; Creatinine; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Methacholine Chloride; Nitric Oxide; Peak Expiratory Flow Rate; Salmeterol Xinafoate

To observe the effect of Fluticasone inhalation combined with Xiaoqinglong decoction (XQLD) on pulmonary function and serum interleukin-16 (IL-16) level in asthma patients.. Fifty-four mild or severe asthma patients were selected and randomly divided into three groups. The treated group was treated with Fluticasone inhalation combined with XQLD, Fluticasone group treated with Fluticasone inhalation, and XQLD group treated with XQLD respectively. Meanwhile ten healthy volunteers were selected as healthy control group. The conventional pulmonary function FEV1 and respiratory impedance R5 were measured before and after 4 weeks treatment. The IL-16 levels were determined by using ELISA.. FEV1 were obviously increased and R5 decreased in the three groups after treatment (P < 0.05 or P < 0.01), but the improvement was more significant in the treated group (P < 0.01). Before treatment, serum levels of IL-16 in all the three groups were significantly higher than those in the healthy control group (P < 0.01) and lowered after treatment respectively, the treated group was significantly lower than those of the other two groups (P < 0.05 or P < 0.01). The serum level of IL-16 was negatively correlated with FEV1 and positively with R5(r1 = -0.67, r2 = 0.71, P < 0.01).. The effects of Fluticasone inhalation combined with XQLD on pulmonary function and serum IL-16 levels were superior to those of Fluticasone inhalation and XQLD alone in asthma patients. So it could become an important therapeutical method in treating mild and severe asthma patients.

Topics: Administration, Inhalation; Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Drugs, Chinese Herbal; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Interleukin-16; Lung; Male; Middle Aged; Phytotherapy; Respiratory Function Tests

To evaluate patient preference, ease of use, and correctness of use of fluticasone propionate administered as inhalation powder via the Diskus (GlaxoSmithKline, Research Triangle Park, NC) and as inhalation aerosol administered via metered-dose inhaler (MDI).. In 154 patients 12 years of age and older with asthma and a history of MDI use, the Diskus and the MDI were compared in a randomized, open-label, 7-week crossover study.. In patients who had used both devices, more found the Diskus easier to use (59%) and preferred it overall (60%) compared with the MDI (P < or = 0.025). Ninety-eight percent (for the MDI) vs 91% (for the Diskus) of patients were able to correctly perform all the maneuvers necessary to use the devices correctly by either viewing a single demonstration and/or reading the instructions for use. Ninety-four percent of all patients found it easier to tell the number of residual doses with the Diskus (P < 0.001), and 59% of patients indicated that they would most likely request the Diskus from their physician (P = 0.025). Compliance was significantly better with the Diskus; 91.1% of patients used the Diskus as directed compared with 78.6% for the MDI (P = 0.013).. In patients exposed to both devices, the majority preferred the Diskus and found it easier to use compared with the MDI. Ninety-one percent of patients used the Diskus correctly with minimal training, and when given a choice, most indicated they would likely request the Diskus from their physicians. Together, these data indicate a significant level of acceptance of the Diskus device in this patient population.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Cross-Over Studies; Female; Fluticasone; Humans; Male; Metered Dose Inhalers; Middle Aged; Patient Satisfaction; Powders

Chronic rhinosinusitis is frequently associated with asthma. A Th2 cytokine pattern has been recently reported in chronic rhinosinusitis in asthmatic children.. To evaluate the effects of treating concomitant chronic rhinosinusitis on respiratory symptoms and function and immunopathological parameters in asthmatic children.. Eighteen children with moderate asthma (age range, 5 to 12 years) poorly controlled by high doses of inhaled corticosteroids and chronic rhinosinusitis were evaluated for symptoms, spirometry, and inflammation at baseline, after treatment, and 1 month after suspension of treatment. All of the children were treated with a combination of amoxicillin and clavulanate (20 mg/kg twice daily) and fluticasone propionate aqueous nasal spray (100 microg/d) for 14 days. A short course of oral corticosteroids was also prescribed (deflazacort, 1 mg/kg daily for 2 days, 0.5 mg/kg daily for 4 days, and 0.25 mg/kg daily for 4 days). Rhinosinusal lavage for cytokine measurements and a nasal scraping for cytologic analysis were performed in all patients before and after medical treatment.. A negative endoscopy result was demonstrated in 15 children after treatment. Symptoms and respiratory function significantly improved after treatment and 1 month later; 8 children had intermittent asthma and 10 had mild asthma. A significant reduction of inflammatory cell numbers was detected in all asthmatic children. Interleukin 4 levels significantly decreased (P < 0.001), whereas interferon-y levels increased (P < 0.001).. Treatment of chronic rhinosinusitis is able to improve symptoms and respiratory function in asthmatic children, reducing inflammatory cells and reversing the cytokine pattern from a Th2 toward a Th1 profile.

Topics: Amoxicillin-Potassium Clavulanate Combination; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Child, Preschool; Drug Therapy, Combination; Endoscopy; Female; Fluticasone; Forced Expiratory Volume; Humans; Interferon-gamma; Interleukin-4; Male; Neutrophils; Pregnenediones; Rhinitis, Allergic, Perennial; Sinusitis

Pharmacokinetic studies can be used to measure lung dose of inhaled drugs. The aim of this study was to compare the lung deposition of budesonide (BUD) inhaled from Turbuhaler (AstraZeneca, Lund, Sweden) and fluticasone propionate (FP) inhaled from Diskus (GlaxoSmithKline, London, UK) and to assess if the study design used for pharmacokinetic studies can be simplified. Plasma levels of BUD and FP were measured for 21 hours on five separate days in 15 patients aged 8 to 14 years: (1) Intravenous infusion of 200 microg BUD, (2) intravenous infusion of 200 microg fluticasone dipropionate, (3) inhalation of 800 microg BUD via Turbuhaler, (4) inhalation of 750 microg FP via Diskus, and (5) inhalation of BUD and FP on the same day. Charcoal was ingested to eliminate drug uptake from the gastrointestinal tract. The mean lung deposition of drug after Turbuhaler and Diskus inhalation was 30.8 and 8.0% when BUD and fluticasone were administered on separate days and 29.5% (BUD) and 7.6% (fluticasone) when the two drugs were inhaled on the same day. Lung deposition is four times higher in children after inhalation from Turbuhaler than after inhalation from Diskus. Pharmacokinetic studies with BUD and FP can be simplified because the two treatments can be administered on the same day.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Asthma; Biological Availability; Bronchodilator Agents; Budesonide; Child; Cross-Over Studies; Female; Fluticasone; Glucocorticoids; Humans; Infusions, Intravenous; Lung; Male; Metered Dose Inhalers; Tissue Distribution

Changes in health-related quality of life (HRQoL) were evaluated in adults with severe asthma following inhaled corticosteroid treatment with high-dose beclomethasone dipropionate or budesonide (BDP/BUD) and compared with fluticasone propionate taken at approximately half the dose of BDP/BUD.. HRQoL was assessed as part of an open, multicentre, randomized, parallel-group study in Australia evaluating the safety and efficacy of switching to fluticasone propionate (FP) 1000-2000 micro g/day (n = 67) compared with remaining on BDP/BUD >/=1750 micro g/day (n = 66) for 6 months. Patients completed two HRQoL questionnaires, the Asthma Quality of Life Questionnaire (AQLQ) and the Medical Outcomes Study Short Form-36 (SF-36), at baseline and at weeks 12 and 24. A change in AQLQ score of >/=0.5 was considered to be clinically meaningful.. There were significant improvements in HRQoL with FP on four of the eight dimensions on the SF-36 (i.e. physical functioning, general health, role-emotional, and mental health), while there were no significant improvements in HRQoL in the BDP/BUD group. Overall, patients in the FP group experienced significantly greater improvement (P < 0.001) in AQLQ scores at weeks 12 and 24 compared with the BDP/BUD group. On the individual domains of the AQLQ, there were significant treatment differences (P < 0.01) in favour of FP in three of the four domains (activity limitations [0.92], symptoms [0.73], and emotional function [1.02]). Mean differences between groups for overall score and these three domains were also clinically meaningful.. Patients with severe asthma who received FP (at approximately half the dose of BDP/BUD) experienced statistically significant, as well as clinically meaningful, improvements in their HRQoL.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Female; Fluticasone; Humans; Male; Quality of Life; Surveys and Questionnaires; Treatment Outcome

Inhaled corticosteroids are established first-line anti-inflammatory treatment for asthma. Clinical trials comparing inhaled corticosteroids must take into consideration that because of their excellent effect at low doses, they typically induce a near-maximal response in asthma patients.. The aim of the present dose-response study was to estimate the minimal effective doses (MEDs) of budesonide and of fluticasone propionate via dry-powder inhaler in adults with mild to moderate asthma.. This was a randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial performed in adults to compare these 2 inhaled corticosteroids. After a 4- to 6-week run-in period with beclomethasone dipropionate 2000 pg/d, patients fulfilling defined criteria for asthma control were randomly allocated to treatment with budesonide or fluticasone, both administered BID at a total of 800 pg/d. At 5-week intervals, the dose was reduced to 400 and then 200 pg/d (200 and 100 pg BID) if asthma control was maintained according to further defined criteria. The MED was defined as the last dose level before deterioration of asthma control.. Subjects were 197 asthmatic patients with a mean age of 40.6 years in the budesonide group and 41.5 years in the fluticasone group. In both groups, baseline mean forced expiratory volume in 1 second (FEV(1)) was 79.4% of the predicted normal volume and baseline mean FEV(1) reversibility was 22.3%. The median MED for both groups was 400 microg/d, with no detectable difference in dis-tributions. The budesonide-to-fluticasone ratio for the geometric mean MED was 123% (95% CI, 99-153 [not significant]). No statistically significant differences regarding lung function, symptom scores, or rescue medication usage were found between the treatment groups during the first treatment period. Adverse-event profiles were similar in both groups, and no unexpected adverse events were considered to be caused by the study drugs.. This effect-controlled study did not detect a statistically significant difference between the MEDs for budesonide and fluticasone via dry-powder inhaler in adults with mild to moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Powders; Time Factors

Low-dose adrenocorticotropin hormone (ACTH) tests (0.5 microg/L 73 m2) were done before and after switching from inhaled beclomethasone dipropionate to inhaled fluticasone propionate in 12 patients 33-77 years old who had mild-to-severe asthma to compare the effects of these drugs on adrenal function. Low-dose ACTH tests were performed after the subjects had received inhaled beclomethasone dipropionate (200-900 microg/day) for at least 12 wk. Treatment was then switched to inhaled fluticasone propionate (200-600 microg/day) for at least 12 wk, and a second low-dose ACTH test was done. Pulmonary function was assessed on the basis of peak expiratory flow rate (PEFR, % of predicted value). After switching treatment, the daily dose of inhaled corticosteroid decreased by about 40%. Basal serum cortisol and ACTH levels were similar with both treatments. The adrenal response, as assessed by incremental rise in the serum cortisol level (peak minus basal) after ACTH challenge, improved significantly (5.6-7.9 microg/dL, p < 0.01) after switching to fluticasone. All three patients who had lower serum cortisol levels during beclomethasone treatment than during fluticasone treatment showed improvement in both the peak cortisol level and the incremental rise in cortisol. Mean morning and evening PEFRs significantly increased after switching from beclomethasone to fluticasone (morning: 71.2 to 76.0%, p < 0.01; evening: 67.3 to 72.1%, both p < 0.05). The diurnal variation of PEFR significantly decreased from 10.9% to 8.3% after switching treatment (p < 0.01). We conclude that switching from beclomethasone to fluticasone reduces the risk of adrenal dysfunction associated with inhaled steroids and improves pulmonary function.

Topics: Administration, Inhalation; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Female; Fluticasone; Humans; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate; Pituitary-Adrenal Function Tests

We wanted to evaluate whether treatment with an inhaled corticosteroid and an inhaled long-acting beta2-agonist is more effective than an inhaled corticosteroid alone for patients using as-needed albuterol who are initiating maintenance treatment.. To compare the efficacy and safety of twice-daily fluticasone propionate (FP) 88 microg and salmeterol 42 microg combined in a chlorofluorocarbon (CFC)-free (hydrofluoroalkane 134a) metered-dose inhaler (MDI) with the individual agents alone, each delivered through an MDI containing CFC propellants, in patient with persistent asthma previously uncontrolled with as-needed short-acting beta2-agonists alone.. Patients with asthma (n = 283) were randomized to twice-daily treatment for 12 weeks with FP 88 microg combined with salmeterol 42 microg (FSC) in a CFC-free MDI or the individual components alone from CFC-containing MDIs.. At endpoint, mean change from baseline in morning predose forced expiratory volume in 1 second was significantly (P < or = 0.016) greater with FSC (0.69 L) compared with FP (0.51 L) or salmeterol (0.47 L). Fewer patients treated with FSC withdrew due to worsening asthma (1%) compared with FP (3%) or salmeterol (8%; P = 0.024). FSC significantly increased (P < or = 0.002) morning and evening peak expiratory flow rate at endpoint (66.5 and 51.5 L/min, respectively) compared with FP (43.0 and 29.9 L/min, respectively) and salmeterol (29.2 and 21.6 L/min, respectively). In addition, asthma symptom scores were reduced, and percentages of days with no asthma symptoms increased in all treatment groups.. Treatment with FSC in a CFC-free MDI is more effective than FP or salmeterol alone in asthma patients who are symptomatic taking short-acting beta2-agonists alone.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Therapy, Combination; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Middle Aged; Salmeterol Xinafoate; Time Factors; Treatment Outcome

In September 2000, the US Food and Drug Administration (FDA) approved the use of Flovent Diskus (FD) [fluticasone propionate; GlaxoSmithKline; Research Triangle Park, NC], which is an orally inhaled, dry-powder corticosteroid, for the maintenance treatment of asthma at dosages of 50 to 1,000 microg administered twice-daily. Once-daily dosage regimens did not receive approval. This article will detail six clinical trials, five of which incorporated comparative once-daily and twice-daily treatment arms of the same nominal dose of FD.. Six 12-week, randomized, double-blind, placebo-controlled studies in patients with mild-to-moderate asthma, including two pediatric asthma trials (patient age, 4 to 11 years) of total daily doses of fluticasone propionate (FP) of 100 or 200 microg, and four adult and adolescent studies of total daily doses of FP of 100, 200, or 500 microg.. Twice-daily dosing was numerically superior to once-daily dosing at the same nominal dose in all comparative studies for the primary end point, change in predose FEV(1). In five trials, the results of the once-daily dosage of FP were statistically indistinguishable from those with placebo. One trial demonstrated the superiority of FP, 500 microg once-daily, over placebo; however, the effect size was half that observed with twice-daily dosing. Once-daily FP dosing showed no advantage in safety or in patient adherence to medication.. In the FDA review of once-daily dosing of the FD regimen, 100 or 200 microg once-daily dosing was not shown to be significantly better than placebo. FP 500 microg once-daily was found to be superior to placebo, but at about one half the effect size as the same nominal dose given bid. No advantage in patient safety or adherence was demonstrated for once-daily administration over twice-daily administration, and once-daily administration is not currently recommended.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Asthma; Bronchodilator Agents; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Fluticasone; Humans; Severity of Illness Index

To assess the effect of montelukast versus salmeterol added to inhaled fluticasone propionate on asthma exacerbation in patients whose symptoms are inadequately controlled with fluticasone alone. Design and setting A 52 week, two period, double blind, multicentre trial during which patients whose symptoms remained uncontrolled by inhaled corticosteroids were randomised to add montelukast or salmeterol.. Patients (15-72 years; n = 1490) had a clinical history of chronic asthma for > or = 1 year, a baseline forced expiratory volume in one second (FEV1) value 50-90% predicted, and a beta agonist improvement of > or = 12% in FEV1.. The primary end point was the percentage of patients with at least one asthma exacerbation.. 20.1% of the patients in the group receiving montelukast and fluticasone had an asthma exacerbation compared with 19.1% in the group receiving salmeterol and fluticasone; the difference was 1% (95% confidence interval -3.1% to 5.0%). With a risk ratio (montelukast-fluticasone/salmeterol-fluticasone) of 1.05 (0.86 to 1.29), treatment with montelukast and fluticasone was shown to be non-inferior to treatment with salmeterol and fluticasone. Salmeterol and fluticasone significantly increased FEV1 before a beta agonist was used and morning peak expiratory flow compared with montelukast and fluticasone (P < or = 0.001), whereas FEV1 after a beta agonist was used and improvements in asthma specific quality of life and nocturnal awakenings were similar between the groups. Montelukast and fluticasone significantly (P = 0.011) reduced peripheral blood eosinophil counts compared with salmeterol and fluticasone. Both treatments were generally well tolerated.. The addition of montelukast in patients whose symptoms remain uncontrolled by inhaled fluticasone could provide equivalent clinical control to salmeterol.

Topics: Acetates; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Fluticasone; Forced Expiratory Volume; Humans; Middle Aged; Quinolines; Salmeterol Xinafoate; Sulfides; Treatment Outcome

Until now, care provided by asthma nurses has been additional to care provided by paediatricians. A study was undertaken to compare nurse led outpatient management of childhood asthma with follow up by a paediatrician.. Seventy four children referred because of insufficient control of persistent asthma were randomly allocated to 1 year follow up by a paediatrician or asthma nurse. The main outcome measure was the percentage of symptom-free days. Additional outcome measures were airway hyperresponsiveness, lung function, daily dose of inhaled corticosteroids (ICS), number of exacerbations, number of additional visits to the general practitioner, absence from school, functional health status, and disease specific quality of life.. There were no significant differences at the end of the 1 year study period between the two treatment groups in percentage of symptom-free days (mean difference 2.5%; 95% CI -8.8 to 13.8), airway hyperresponsiveness (log10 PD20 0.06; -0.19 to 0.32), functional health status (10.1; -0.3 to 19.8), disease specific quality of life of patients (0.08; -0.9 to 0.7), and disease specific quality of life of caregivers (0.09; -0.2 to 0.3), nor in any other outcome parameters. Most outcome parameters improved considerably over the 1 year study period. These improvements were achieved although the daily dose of ICS was reduced by a mean of 26% compared with the dose received by children at referral. All parents were satisfied with the asthma care received.. After initial assessment in a multidisciplinary clinic, childhood asthma can be successfully managed by an asthma nurse in close cooperation with a paediatrician. During close follow up by paediatrician or asthma nurse, asthma control improved despite a reduction in ICS dose.

Topics: Adolescent; Ambulatory Care; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Consumer Behavior; Female; Fluticasone; Follow-Up Studies; Health Status; Humans; Infant; Male; Netherlands; Parents; Pediatrics; Quality of Life; Treatment Outcome

The circadian variation in urinary leukotriene E(4) (LTE(4)) excretion with a morning acrophase has recently been reported in nocturnal asthma (NA); however, the effects of inhaled corticosteroids (ICS) on this circadian rhythmicity of leukotriene (LT) in patients with NA are controversial.. We first measured peak expiratory flow (PEF), urinary LTE(4), 11-dehydro-thromboxane B(2) (TXB(2)), and creatinine levels six times every 4 h for 24 h in two groups: patients with mild-to-moderate, steroid-naive NA (n = 10, group A), and patients with severe NA treated with high-dose ICS (n = 10, group B). Next, group A patients received 2 weeks of treatment with 800 microg/d of inhaled fluticasone propionate (FP), and we compared the measured parameters before and after treatment.. In group A, a circadian rhythm in urinary LTE(4) with peak levels at approximately 4 AM associated with reduced PEF was observed. Group B had suppression of urinary LTE(4) excretion and had no circadian rhythmicity, as seen in group A, despite a dip in PEF at 4 AM. A high dose of FP in group A significantly (p < 0.05) reduced LTE(4) levels and abolished the circadian rhythm, as well as improving PEF. We found no significant difference in the circadian rhythm of urinary 11-dehydro-TXB(2) between groups A and B, and high-dose FP partially decreased urinary 11-dehydro-TXB(2) levels but not significantly.. A high-dose of ICS reduced urinary LTE(4) levels and abolished their circadian variation in patients with asthma, suggesting that LT might contribute to the mechanism of NA.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Circadian Rhythm; Creatinine; Female; Fluticasone; Glucocorticoids; Humans; Leukotriene E4; Male; Middle Aged; Peak Expiratory Flow Rate; Thromboxane B2

Patients with asthma experience disruptions in usual activities that can impair their quality of life, and in patients whose daily routine involves an active lifestyle, these disruptions can be severe. We assessed the patient-perceived effect of treatment with fluticasone propionate/salmeterol combination (FSC), compared with fluticasone propionate (FP) or salmeterol (SAL) alone, on activity limitations, particularly strenuous physical activities. The Asthma Quality of Life Questionnaire (AQLQ) was administered in two 12-week, randomized, double-blind, placebo-controlled trials comparing FSC 100/50 or 250/50 microg twice daily vs. the individual components alone in 686 adults and adolescents with asthma. In one study, patients were stratified by prior treatment [low to medium doses of inhaled corticosteroids (ICS) or SAL], and in the other study, all patients were previously treated with medium to high doses of ICS. Patients prospectively identified five activities they performed regularly and were asked how these activities were limited by their asthma. The effect of randomized treatment on strenuous activities (e.g., aerobics, cycling, hiking, and basketball) was assessed. In both studies, treatment with FSC resulted in clinically meaningful improvements (i.e., change in AQLQ of > or = 0.5) and was statistically significantly better than SAL in both studies and FP in one study. Treatment of the two main components of asthma--inflammation and bronchoconstriction--with FSC results in clinically meaningful improvements in the ability of patients with persistent asthma to perform not only their usual activities but also strenuous activities.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Exercise Tolerance; Female; Fluticasone; Humans; Male; Quality of Life; Salmeterol Xinafoate; Surveys and Questionnaires

Regular anti-inflammatory treatment is essential in treating persistent asthma. Most commonly, inhaled corticosteroids (ICS) are used. However, especially in children, there is concern about the long-term safety of ICS such that doses should be kept to a minimum. The use of theophylline has decreased because of frequent side-effects in therapeutic doses. In adults, there have been reports about an immunomodulatory effect of low-dose theophylline. To study the clinical and immunomodulatory effect in children, 36 patients (mean age 12.5 SD 2.4 years) with moderate, persistent asthma on regular ICS were recruited into a placebo-controlled, double-blind study. After a 6-week run-in period, patients received either theophylline 10 mg/kg bodyweight or placebo for 12 weeks. Diary cards, lung function, peripheral blood lymphocyte subpopulations and serum eosinophil cationic protein (sECP) were assessed. In the treatment group, mean serum theophylline was 7.1 mg/l. There was no change in symptoms or use of rescue medication. Mean (SD) peak expiratory flow (PEF) increased from 86% (24) to 95% (18) predicted. sECP decreased from 43.2 microg/l (32.5) to 26.5 microg/l (16.9) (p = 0.02). Lymphocyte subpopulations did not change. The study failed to show a beneficial clinical or an immunomodulatory effect of theophylline when used in low doses. These results do not support a more important role of theophylline in the long-term treatment of moderate childhood asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Airway Resistance; Androstadienes; Antigens, Differentiation, T-Lymphocyte; Asthma; Biomarkers; Blood Proteins; Bronchodilator Agents; Budesonide; Child; Child Welfare; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophil Granule Proteins; Female; Fluticasone; Forced Expiratory Volume; Germany; Humans; Lymphocyte Count; Lymphocyte Subsets; Male; Peak Expiratory Flow Rate; Predictive Value of Tests; Respiratory Function Tests; Ribonucleases; School Health Services; T-Lymphocytes; Theophylline; Time; Treatment Outcome; Vital Capacity

Inhalers combining long acting beta2-adrenoceptor agonists (LABA) and corticosteroids (ICS) are indicated at Step 3 of current asthma guidelines. We evaluated the relative effects of LABA + ICS combination vs ICS alone on pulmonary function, bronchoprotection, acute salbutamol recovery following methacholine bronchial challenge, and surrogate inflammatory markers in patients with moderate persistent asthma.. Twenty-nine patients with mean FEV1 (+/- SEM) of 78 +/- 3% predicted completed a randomized, double-blind, double-dummy, cross-over study. Patients received either 4 weeks of budesonide 400 microg + formoterol 12 microg (BUD + FM) combination twice daily followed by 1 week of BUD 400 microg alone twice daily, or 4 weeks of fluticasone propionate 250 microg + salmeterol 50 microg (FP + SM) combination twice daily followed by 1 week of FP 250 microg alone twice daily. Measurements were made at baseline and following each randomized treatment.. FEV1 increase from pretreatment baseline as mean (+/- SEM) % predicted was significantly higher (P < 0.05) for BUD + FM (8 +/- 1%) vs BUD (2 +/- 1%), and for FP + SM (8 +/- 1%) vs FP (2 +/- 1%). The fall in FEV1 following methacholine challenge as percentage change from prechallenge baseline FEV1 was not significantly different in all four groups; BUD + FM (22 +/- 1%), BUD (24 +/- 1%), FP + SM (23 +/- 1%) and FP (23 +/- 1%). Salbutamol recovery over 30 min following methacholine challenge as area under curve (AUC %.min) was significantly blunted (P < 0.05) with BUD + FM (486.7 +/- 35.5) vs BUD (281.1 +/- 52.8), and with FP + SM (553.1 +/- 34.1) vs FP (368.3 +/- 46.7). There were no significant differences between respective combination inhalers or between respective ICS alone. Decreases in exhaled nitric oxide (NO) and serum eosinophilic cationic protein (ECP) from baseline were not significantly different between treatments.. Combination inhalers improve pulmonary function without potentiating anti-inflammatory effects on exhaled NO and serum ECP as compared with ICS alone, but delay acute salbutamol recovery after bronchoconstriction.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Biomarkers; Bronchi; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate

Immunotherapy is a recognized treatment for allergic respiratory diseases.. To study the usefulness of immunotherapy in combination with optimal pharmacological therapy.. Thirty-eight children (8-14 years) suffering from seasonal asthma+/-rhinoconjunctivitis due to Parietaria poorly controlled by anti-allergic drugs treatment were selected. After randomization according to a double-blind placebo-controlled design they received active sublingual immunotherapy (15 children) or placebo (15 children) for 13 months combined with inhaled fluticasone twice a day during the pollen season. Eight children were taken as control, whereas all patients were instructed to take symptomatic drugs on need. Early and late skin response to the allergen were assessed in all patients before and after treatment. Drug and symptom scores, as well as visual analogue scores (VASs) and Parietaria pollen counts were assessed during the pollen season.. Groups were well balanced for age, gender, early and late skin response before treatment. Four children dropped out, in one case in relationship with active sublingual immunotherapy (SLIT) administration. Chest and nose symptoms, as well as drug scores and VASs were significantly better in both the active or placebo SLIT+fluticasone (S+F) as compared to the control group (P between <0.001 and 0.043). Eye symptoms were significantly better in the active S+F group as compared to control (P=0.025). The VASs were significantly better in the active S+F group as compared to the placebo S+F group (P=0.037). The early skin response decreased significantly in the active S+F group (P<0.001), whereas the late skin response changed significantly in all groups, with an increase in the placebo+fluticasone group (P=0.019) and in the control group (P=0.037) and a decrease (P<0.0001) in the active S+F group.. The clinical efficacy of S+F is equal to that of fluticasone alone, but the addition of SLIT has effects also on non-bronchial symptoms.

Topics: Administration, Inhalation; Administration, Sublingual; Adolescent; Allergens; Androstadienes; Anti-Allergic Agents; Asthma; Child; Combined Modality Therapy; Desensitization, Immunologic; Double-Blind Method; Female; Fluticasone; Humans; Male; Parietaria; Plant Proteins; Pollen; Rhinitis, Allergic, Seasonal; Skin; Treatment Outcome

It is now recommended to add an inhaled long-acting beta 2-agonist, or as an alternative, to add a leukotriene-antagonist, in patients whose asthma is insufficiently controlled with an inhaled corticosteroid alone. A randomised, multicentre, open-label, parallel-group study was carried out in 246 patients of at least 15 years, whose asthma was not adequately controlled with a medium dose of an inhaled corticosteroid. They received either fluticasone/salmeterol combination 250/50 micrograms one inhalation twice daily or CFC beclomethasone dipropionate 250 micrograms two puffs twice daily plus montelukast 10 mg in the evening for 12 weeks. The mean morning PEFR (main criterion) was significantly (p = 0.017) more improved with fluticasone/salmeterol (+44.2 L/min) than with beclomethasone dipropionate plus montelukast (+31.0 L/min). Other outcomes showed significantly better improvements (p 0.022 Pound) with fluticasone/salmeterol than with beclomethasone plus montelukast. The two treatments were well tolerated. Fluticasone/salmeterol provided a better asthma control than beclomethasone dipropionate plus montelukast in patients insufficiently controlled with an inhaled corticosteroid alone.

Topics: Acetates; Administration, Inhalation; Adult; Aerosols; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Cyclopropanes; Drug Combinations; Female; Fluticasone; Humans; Leukotriene Antagonists; Male; Middle Aged; Peak Expiratory Flow Rate; Powders; Prospective Studies; Quinolines; Salmeterol Xinafoate; Sulfides; Treatment Outcome

The efficacy and safety of Symbicort (budesonide and formoterol in a single inhaler) were compared with those of a high dose of the commonly used corticosteroid fluticasone propionate in patients with moderate persistent asthma.. This randomized, double-blind, double-dummy, parallel-group study involved 373 patients with asthma (mean age 42 years; FEV(1) 78% of predicted; reversibility 21%). After a 2-week run-in period, during which patients received budesonide 200 microg twice daily, they were randomly assigned to treatment with either Symbicort Turbuhaler (budesonide/formoterol 160/4.5 microg, one inhalation twice daily) or Flovent/Flixotide Diskus (fluticasone propionate 250 microg twice daily) for 12 weeks.. Significantly greater increases in morning PEF, the primary efficacy variable, were observed in patients treated with budesonide/formoterol compared with fluticasone propionate (27.4 L/min vs 7.7 L/min; p < 0.001). Evening PEF and clinic FEV(1) also favored budesonide/formoterol compared with fluticasone propionate (p < 0.001), as did use of reliever medication (p = 0.04) and the proportion of reliever-free days (p < 0.001). There were also numerical improvements in symptom-free days (60.4% vs 55.5%), night-time awakenings (7.9% vs 9.6%) and asthma-control days (57.8% vs 52.4%) in favor of budesonide/formoterol. The risk of an exacerbation was reduced by 32% in the budesonide/formoterol group compared with the fluticasone propionate group (p < 0.05). Both treatments were well tolerated.. Symbicort (budesonide/formoterol in a single inhaler) was more effective than a high dose of fluticasone propionate in improving lung function, reducing use of reliever medication and improving control of moderate persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Respiratory Function Tests; Treatment Outcome

Neurokinin (NK) A causes airway narrowing in patients with asthma through direct and indirect mechanisms. The effects of the inhaled glucocorticosteroid fluticasone propionate (FP) on the bronchial responsiveness to NKA and methacholine were studied. Patients (n=11) with mild asthma participated in a randomized, double-blind, placebo-controlled crossover trial. FP (500 microg b.i.d.) or matched placebo was administered via Diskhaler for 14 days. Bronchial challenges were performed on days 1 and 13 (methacholine) and 0 and 14 (NKA) for each treatment period. At the active treatment period, the mean log2 provocative concentration causing a 20% fall in the forced expiratory volume in one second (PC20)+/-SEM for NKA was -12.72+/-0.63 at the beginning and -9.77+/-0.49 at the end of the period (p<0.0001), while under placebo, it was -12.16+/-0.82 and -12.19+/-0.51 respectively (NS). At the active treatment period, the mean log2 PC20 for methacholine was -5.25+/-0.40 at the beginning and -4.22+/-0.31 at the end of the period (p=0.012), while under placebo, it was -5.47+/-0.47 and -5.24+/-0.42 respectively (NS). The reduction in response to NKA was significantly larger than that for methacholine. A 2-week course of an inhaled steroid reduces bronchial responsiveness to neurokinin A, an effect more pronounced than the reduction in bronchial responsiveness to methacholine.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Asthma; Bronchial Hyperreactivity; Bronchoconstriction; Bronchoconstrictor Agents; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Neurokinin A

Children with persistent mild to moderate bronchial asthma require anti-inflammatory therapy. According to current treatment guidelines both sodium cromoglycate (SCG) and inhaled corticosteroids can be used. If children remain symptomatic despite regular SCG therapy, corticosteroids are the next therapeutic option.. To determine whether combined SCG and fluticasone (inhaled corticosteroid) therapy is of additional benefit in children who are symptomatic on SCG compared with simply switching to fluticasone.. Children with mild or moderate persistent asthma aged 6 to 16 years who had been treated with inhaled SCG for at least 3 months prior to the study received either 2 mg SCG four times daily from a metered dose inhaler plus fluticasone propionate powder 50 microg b.i.d. from the Diskus inhaler (group FS) or fluticasone 50 microg b.i.d. only (group F). The randomised, controlled, parallel-group study had a 2 week run-in phase and an 8 week treatment period. Morning and evening peak expiratory flow rates (PEFR) were measured daily by patients and recorded in diaries. Asthma symptoms, use of rescue medication and spirometry were also documented.. Paediatricians from 21 study centres recruited 124 children with asthma, of whom 104 fulfilled randomisation criteria and were allocated to study medication. Morning PEFR increased by 47 l/min and by 45 l/min after 8 weeks of treatment in groups F and FS, respectively. The adjusted difference between groups was 0.84% of predicted (95% CI, -7.3 to 5.6, p=0.80). Asthma symptoms and lung function also improved with no significant differences between treatment groups (p>0.24). Frequency and severity of adverse events was similar in both groups.. In children who are symptomatic while taking sodium cromoglycate four times daily, the combination of inhaled fluticasone and SCG is not superior to fluticasone alone. SCG can safely be withdrawn when commencing fluticasone, thus facilitating asthma treatment.

Topics: Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Cromolyn Sodium; Drug Therapy, Combination; Fluticasone; Humans; Hydrocortisone; Prospective Studies; Respiratory Function Tests

To compare the therapeutic ratio of chlorofluorocarbon (CFC) and hydrofluoroalkane-134a (HFA) formulations of fluticasone propionate (FP).. We performed a randomized, placebo-controlled, crossover study comparing 6 weeks of treatment with FP using 500 micro g/d and 1,000 microg/d formulations of CFC and HFA. The primary end points were provocative dose of methacholine causing a 20% fall in FEV1 (PD20) and overnight urinary cortisol/creatinine excretion.. Eighteen patients with mild-to-moderate asthma and geometric mean (SEM) PD20 of 82.3 micro g (19.2 micro g) completed the study. All treatments significantly improved PD20 values and morning peak expiratory flow vs placebo, while 1,000 microg/d was significantly better than 500 microg/d for the CFC formulation of FP (CFC-FP) but not the HFA formulation of FP (HFA-FP). Only 1,000 microg/d of CFC-FP caused significant suppression of overnight urinary cortisol/creatinine compared to placebo. There were no differences between formulations at either dose.. The increased airway benefit with CFC-FP > 500 microg/d was offset by greater systemic effects. Although HFA-FP had fewer systemic effects than CFC-FP at 1,000 microg/d, there was no benefit to increasing HFA-FP to > 500 microg/d.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aerosol Propellants; Androstadienes; Anti-Inflammatory Agents; Asthma; Chlorofluorocarbons; Cross-Over Studies; Female; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Male; Single-Blind Method

To determine if differences between holding chambers in previous in vitro aerosol studies would agree with the bioavailability of inhaled fluticasone propionate between the same holding chambers in children with asthma.. Double-blind, randomized, crossover study. University of Florida Clinical Research Center.. Eight children (aged 5-9 yrs) with stable asthma.. Under observation, the children inhaled two 110-microg puffs of fluticasone twice/day through the InspirEase or E-Z Spacer holding chamber.. Blood samples were collected at baseline and then at 0.5, 1, 1.5, 2, 4, and 6 hours after the last dose of fluticasone. Primary outcome measures were peak fluticasone steady-state plasma concentration (Cmax) and area under the fluticasone plasma concentration-time curve from 0-6 hours (AUC0-6). The fluticasone plasma concentrations were determined by high-performance liquid chromatography-mass spectrometric assay. Mean +/- SD Cmax from InspirEase (245 +/- 77 pg/ml) was 18% higher than that after E-Z Spacer (199 +/- 58 pg/ml, p < 0.05). Mean +/- SD AUC0-6 from InspirEase (1103 +/- 305 pg x hr(-1) x ml(-1) was 22% higher than that delivered from E-Z Spacer (863 +/- 258 pg x hr(-1) x ml(-1), p = 0.06).. Differences in inhaled fluticasone bioavailability between these holding chambers in children with asthma corroborate differences reported in earlier in vitro aerosol studies.

Topics: Administration, Inhalation; Aerosols; Androstadienes; Area Under Curve; Asthma; Biological Availability; Bronchodilator Agents; Child; Child, Preschool; Cross-Over Studies; Double-Blind Method; Fluticasone; Humans; Male; Nebulizers and Vaporizers

Although inhaled corticosteroids are the most effective anti-inflammatory agents available for the treatment of asthma, they have, at best, only modest effects on airways responsiveness to methacholine. Thus, hyper-responsiveness to methacholine is a relatively insensitive monitor of the effectiveness of glucocorticoids in asthmatic subjects.. The study aimed to determine if airways hyper-responsiveness to bradykinin provides a more sensitive index of glucocorticoid responsiveness in asthmatic subjects than does hyper-responsiveness to methacholine.. A double-blind, placebo-controlled, parallel group study comparing the effects of inhaled fluticasone (220 micro g twice daily) on responsiveness to the two stimuli in asthmatic subjects who had never previously received corticosteroid therapy. Drug (n = 13) or placebo (n = 12) were administered for 16 weeks. Responsiveness to bradykinin and methacholine was determined at baseline and at 4 week intervals.. Placebo did not alter responsiveness to either stimulus compared to baseline. Fluticasone treatment significantly reduced responsiveness to bradykinin (P < 0.001 by Friedman anova) and methacholine (P = 0.02), but changes in responsiveness to bradykinin were significantly greater than those in methacholine responsiveness (P = 0.002). Bradykinin responsiveness was decreased at all treatment times compared to baseline, while methacholine responsiveness was not decreased until 8 weeks of therapy. When data were analyzed as changes from baseline (DeltaLog PD20), DeltaLog PD20 for methacholine was not different at any time-point between the two treatment groups. By contrast, DeltaLog PD20 for bradykinin was significantly greater in patients receiving fluticasone compared to those on placebo at all but the 16-week treatment time. Ten of 13 subjects receiving fluticasone failed, on at least one post-treatment visit, to show a 20% fall in forced expiratory volume (FEV1), even at the highest dose of bradykinin.. Airways responsiveness to bradykinin is more profoundly, and more rapidly, reduced by inhaled glucocorticoids than is responsiveness to methacholine. Airways hyper-responsiveness to bradykinin provides a convenient and sensitive monitor of glucocorticoid responsiveness in asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Analysis of Variance; Androstadienes; Asthma; Bradykinin; Bronchial Provocation Tests; Bronchoconstrictor Agents; Depression, Chemical; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Lung; Male; Methacholine Chloride; Middle Aged; Vasodilator Agents

The aim of this study was to compare the effect of 7 days nebulised fluticasone propionate (FP) with oral prednisolone on 24-h urinary-free cortisol excretion, systemic exposure and safety. This was a randomised, double-blind, double-dummy, two-way crossover study. Thirty-one children (19 male, 12 female, mean age 8 years) with stable asthma were randomly assigned to 7 days treatment with either FP Nebules (2 x 0.5 mg/2 ml bd) or prednisolone tablets once daily (2 mg/kg/day for 4 days [maximum 40 mg] followed by 1 mg/kg/day or half the original dose for 3 days [maximum 20 mg]). After a 2-4 week washout period, patients received the second treatment for 7 days, followed by a 2-week follow-up visit. The primary outcome measure was 24-h urinary-free cortisol concentrations corrected for creatinine. Nebulised FP (1 mg bd) had significantly less effect on 24-h urinary-free cortisol excretion than oral prednisolone (8.9 ng/ml for FP and 5.0 ng/ml for prednisolone, P = 0.001). Systemic exposure to FP was also low. In conclusion, FP Nebules had significantly less effect on hypothalamic-pituitary-adrenal axis function than oral prednisolone in asthmatic children when used at doses recommended for the treatment of an acute exacerbation of asthma.

Topics: Administration, Inhalation; Administration, Oral; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Prednisolone; Treatment Outcome

Previous studies have indicated the benefits of adding long acting beta(2) agonists to inhaled corticosteroids in the maintenance treatment of moderate to severe asthma. The effects of adding eformoterol to corticosteroids on asthma control and exacerbations in patients with mild to moderate asthma were studied.. After a run in period of 7-14 days on existing medication, 663 symptomatic patients were randomised to receive budesonide Turbohaler 400 microg twice daily together with either eformoterol Turbohaler 9 micro g (delivered dose) or placebo twice daily. After 4 weeks patients whose asthma was well controlled (n=505) were re-randomised to receive budesonide 400 microg daily and either eformoterol 9 micro g or placebo twice daily for a further 6 months.. Patients receiving eformoterol achieved asthma control 10 days sooner than those receiving budesonide alone, and improvements in lung function, symptoms, quality of life, and relief beta(2) agonist use were significantly greater with eformoterol. During the 6 month follow up the frequency of mild exacerbations was significantly lower in the eformoterol group than in those receiving budesonide alone (7.2 versus 10.5 per patient, 95% confidence interval for ratio 0.49 to 0.96, p=0.03). The time to first day of poorly controlled asthma was 97 days in the eformoterol group compared with 42 days in the placebo group (p=0.003).. Adding eformoterol to a low or moderate dose of budesonide in mild asthma resulted in faster and more effective control than treatment with budesonide alone. Eformoterol allowed the corticosteroid dose to be reduced while also decreasing the rate of mild exacerbations compared with budesonide alone. These data suggest a therapeutic advantage of adding eformoterol to inhaled corticosteroids in patients with mild to moderate asthma.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Quality of Life; Survival Analysis; Treatment Outcome

With the transition to hydrofluoroalkane-134a propellants in metered dose inhalers, it is important to consider the efficacy and safety profiles of formulations containing inhaled corticosteroids. We examined the airway and systemic effects of hydrofluoroalkane-134a fluticasone propionate (FLU-HFA) and beclomethasone dipropionate (BEC-HFA) at recommended labelled doses.. Twenty mild to moderate asthmatics were randomised in crossover fashion to receive 6 weeks of 500 micro g/day followed by 1000 micro g/day FLU-HFA and BEC-HFA. Measurements were made at baseline after placebo run in and washout, and after each randomised treatment. The primary airway outcome for benefit was the dose of methacholine provoking a fall in forced expiratory volume in 1 second (FEV(1)) of 20% or more (methacholine PD(20)) and for systemic adverse effects was overnight urinary cortisol/creatinine (OUCC).. For mean responses, both doses of BEC-HFA and FLU-HFA produced significant improvements in PD(20) compared with baseline. The improvement was not significantly greater with 1000 micro g/day FLU-HFA versus BEC-HFA, a 1.69 fold difference (95% CI 0.94 to 3.04). Both doses of BEC-HFA but not FLU-HFA caused significant suppression of OUCC compared with baseline, with significantly (p<0.05) lower values at 1000 micro g/day for BEC-HFA versus FLU-HFA (1.97 fold difference (95% CI 1.28 to 3.02)).. There was no difference in the airway and systemic effects in patients with mild to moderate asthma between FLU-HFA and BEC-HFA at a dose of 500 micro g/day. At 1000 micro g/day there was increased systemic bioactivity with BEC-HFA compared with FLU-HFA, without any gain in airway efficacy.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchoconstrictor Agents; Bronchodilator Agents; Creatinine; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Fluticasone; Forced Expiratory Flow Rates; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Methacholine Chloride

The aim of this prospective, self-controlled, single-blind study was to assess the effect of montelukast added to maintenance therapy with inhaled corticosteroids (ICS) on fractional exhaled nitric oxide (FENO) in asthmatic children. Thirty-five children (age 11.2+/-0.4 yrs (mean+/-SEM)) with mild-to-moderate persistent asthma treated with low to medium doses of ICS and FENO > 20 parts per billion (ppb) were included. The patients were randomly assigned to two groups: 17 patients continued ICS (group C) and 18 had montelukast added to ICS for 3 weeks (group M). FENO measurements were performed in both groups at baseline (T1) and after 3 weeks (T2), and in group M also after 2 weeks of washout. FENO was measured by a chemiluminescence analyser using an on-line method (50 mL x s(-1)) with nitric oxide-free air. The overall mean daily dose of ICS was equivalent to 530+/-58 microg x day(-1) of beclomethasone in group M and to 564+/-55 microg x day(-1) of beclomethasone in group C. There were no significant differences in baseline FENO and forced expiratory volume in one second (FEV1) between the two groups. After 3 weeks there was a significant reduction of FENO values in patients of group M (T1 52.2+/-7.8 ppb, T2 36.1+/-4.6 ppb) but no significant changes in group C (T1 43.5+/-6.0 ppb, T2 47.8+/-9.4 ppb). In group M after 2 weeks of montelukast withdrawal, FENO rose to baseline values (55.6+/-8.7 ppb). In conclusion, after montelukast treatment there is a fractional exhaled nitric oxide reduction in asthmatic children receiving maintenance therapy with inhaled corticosteroids. This suggests an anti-inflammatory effect of montelukast additive to that of inhaled corticosteroids.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Breath Tests; Budesonide; Child; Cyclopropanes; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Maximal Midexpiratory Flow Rate; Nitric Oxide; Prospective Studies; Quinolines; Single-Blind Method; Sulfides

CysLT(1) antagonists are effective for a subset of patients with asthma; however, there has been no good way to predict a given patient's response. We examined the interaction between the clinical response to a cysLT(1) antagonist, pranlukast, and DNA sequence variant A(-444)C in leukotriene C(4) synthase (LTC(4) S) gene in Japanese patients with moderate asthma. The frequency of LTC(4) S C(-444) allele was 21.6% in the Japanese general population (n = 171) and 19.4% in the asthmatic subjects ( n= 349). A 4-week prospective, open trial of pranlukast (225 mg twice daily) was performed in 50 patients with moderate asthma who had been well controlled with inhaled corticosteroid (beclomethasone 400-800 microg/day or fluticasone 200-400 microg/day). The C(-444) allele carriers (n = 16) responded better to pranlukast compared to the A(-444) allele homozygotes ( n= 31) [14.3 5.3% vs. 3.1 2.4% improvement of forced expiratory volume in one second (FEV(1) ), 0.01], while LTC(4) S genotype-stratified response to inhaled beta-agonist salbutamol (200 microg) was not observed (17.5 2.1% vs. 18.7 2.2% improvement of FEV(1) ). Univariate analysis demonstrated that the better response to pranlukast (more than 10% improvement of FEV(1) ) was correlated with LTC(4) S genotype (P < 0.01) and pretreatment airway reversibility to salbutamol (P < 0.01), but not with sex, age, atopic status, urinary leukotriene E(4) excretion rate, or daily dose of inhaled corticosteroid. Furthermore, multivariate regression analysis suggested that LTC(4) S genotype and the bronchodilatory effect of salbutamol were independent variables to predict the clinical response to pranlukast (P < 0.05). We conclude that LTC(4) S genotype is predictive of the clinical response to a cysLT(1) antagonist, pranlukast, in Japanese patients with moderate asthma.

Topics: Administration, Inhalation; Adult; Albuterol; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Asian People; Asthma; Beclomethasone; Chromones; Female; Fluticasone; Forced Expiratory Volume; Genetic Carrier Screening; Glutathione Transferase; Humans; Japan; Leukotriene Antagonists; Male; Middle Aged; Polymorphism, Single Nucleotide; Promoter Regions, Genetic

The present study demonstrates the equivalent efficacy for BDP 500 microg bid given via MDI with the new HFA-134a propellant (Chiesi Farmaceutici S.p.A., Parma) compared to a conventional CFC propellant (Becotide, Allen & Hanburys, UK). One hundred and sixteen adult patients with stable mild to moderate asthma (FEV1 > or = 60% of predicted normal) entered a 2-week run-in period where they maintained their own inhaled corticosteroids and were then assigned to a 12-week treatment with the test drug in a randomized, multicentre, double-blind, double-dummy, parallel-group design. Ninety-one patients completed the study period. Morning and evening peak expiratory flow rate (PEFR), use of rescue salbutamol, number of daytime and nighttime asthma attacks, number of nighttime awakenings, and clinical symptoms were recorded daily by patients on a diary card. Pulmonary function tests (FEV1, FVC, PEFR, MEF50 and FEF25) were completed at study entry, at the start of treatment and every 2 weeks thereafter. Morning (08.00-10.00 AM) serum cortisol was measured at the start and at the end of treatment. Adverse events were collected for the total study period. Equivalence between groups was demonstrated for the primary end-point morning PEFR, as well as for evening PEFR and FEV1 (the 95% CI of the treatments' difference was within the 5% of the LSM of BDP CFC). The other secondary pulmonary function tests measured at the clinic visit showed a satisfactory asthma control, albeit without statistically significant differences between groups. Decreases in the use of rescue salbutamol and in clinical symptoms were also reported in both groups, with no differences between them. Adverse events were reported in 81.4% of patients in the BDP HFA group and in 82.5% in the CFC group. There were 73 and 59 adverse drug reactions in the two groups, respectively; the difference was mainly due to differences in taste. No drug-related serious adverse events were reported in either group. No difference was seen for morning serum cortisol between baseline and end of treatment, or between groups. In conclusion, the BDP-HFA 134a formulation proved to be statistically equivalent to the standard BDP CFC product over 12 weeks in adult patients with mild to moderate asthma.

Topics: Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Chemistry, Pharmaceutical; Chlorofluorocarbons; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Least-Squares Analysis; Male; Middle Aged; Patient Compliance; Peak Expiratory Flow Rate; Severity of Illness Index; Treatment Outcome; United Kingdom; Vital Capacity

Asthma is characterized by eosinophilic airways inflammation with elevated levels of IL-4, IL-5 and sICAM-1, and reduced levels of IL-10 and IFN-gamma. Inhaled corticosteroids powerfully reduce airways inflammation.. To investigate if eosinophil counts, serum eosinophilic cationic protein (ECP) and sICAM-1 levels, as well as serum and production of cytokines (IL-4, IL-5, IL-10, IFN-gamma) by peripheral blood monocytes (PBMCs) are useful markers to monitor therapy with inhaled fluticasone propionate (FP) in asthmatic children.. In a double-blind, 1-year study, 55 asthmatic children (aged 6-10 years) stopped inhaled corticosteroids for a mean period of 24 days and were randomized to receive either FP 200 microg/day (constant dose group), or a starting dose of FP 1000 microg/day with two monthly reductions to 500, 200 and 100 microg/day (stepdown group). Hyper-responsiveness, symptom scores and blood sampling were performed at 2-month intervals.. Symptoms and hyper-responsiveness improved significantly in both treatment groups after reintroduction of FP. Eosinophil counts decreased significantly more during the first 2 months of FP in the stepdown group than in the constant dose group (P = 0.03). We found a trend towards a dose-dependent response in changes of eosinophil counts and serum ECP levels during treatment. Serum IL-4 and IL-5 levels were undetectable in the majority of children. No significant effect of the dose of FP on the release of IL-4, IL-5, IL-10 or IFN-gamma by Con A stimulated PBMCs was found. sICAM-1 levels did not significantly differ at any time point between the two groups.. Serum ECP as well as peripheral blood eosinophils, cytokine production by PBMCs and sICAM-1 levels are insensitive markers in titrating and monitoring therapy with inhaled corticosteroids over a wide dose range in childhood asthma.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Asthma; Biomarkers; Blood Proteins; Bronchial Hyperreactivity; Cell Adhesion Molecules; Child; Cytokines; Double-Blind Method; Drug Administration Schedule; Eosinophil Granule Proteins; Eosinophils; Female; Fluticasone; Glucocorticoids; Humans; Immunoglobulin E; Interferon-gamma; Interleukin-10; Interleukin-4; Interleukin-5; Leukocyte Count; Male; Ribonucleases

Inhaled adenosine 5'-monophosphate (AMP) has an "indirect" bronchoconstrictive effect through mast cell degranulation and mediator release, whereas inhaled histamine has a "direct" effect on smooth muscle. Prolonged treatment with inhaled glucocorticosteroids attenuates airway responsiveness (AR) to AMP and histamine. We investigated the early effects of inhaled fluticasone propionate (FP) therapy on AR in 3 consecutive double-blind, randomized, placebo-controlled crossover studies in steroid-naive subjects with mild asthma. In one study, each of 12 subjects received FP 1000 microg or matched placebo for 7 inhalations at 12 hourly intervals; AR to AMP and FEV(1) were measured 2 hours after the 3rd and 7th inhalations. In a second study, each of 12 subjects received FP 100, 250, or 1000 microg or matched placebo for 3 inhalations at 12 hourly intervals; AR to AMP and FEV(1) were measured 2 hours after the 1st and 3rd inhalations. In a third study, each of 8 subjects received a single inhalation of FP 1000 microg or matched placebo; AR to histamine was measured 2 hours later. In the first study, FP 1000 microg significantly attenuated AR to AMP by 2.7 and 2.5 doubling doses after 3 and 7 inhalations, respectively (P < or =.0001). In the second study, FP 100, 250, and 1000 microg significantly attenuated AR to AMP by 1.9, 2.2, and 2.7 doubling doses, respectively, after 1 inhalation and by 2.4, 2.2, and 3.2 doubling doses, respectively, after 3 inhalations (P < or =.0001); a small but significant increase in FEV(1) (>0.15 L) was observed after 3 inhalations but not after 1 inhalation of FP irrespective of dose (P < or =.05). In the third study, a single inhalation of FP 1000 microg had no effect on AR to histamine. We have demonstrated a reduction in AR to AMP but not AR to histamine within 2 hours of a single inhalation of FP. This reflects a rapid, topical anti-inflammatory action of inhaled FP by a mechanism of action that remains unknown.

Topics: Adenosine Monophosphate; Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchi; Bronchoconstrictor Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Fluticasone; Forced Expiratory Volume; Histamine; Humans; Time Factors

To compare the relative cost effectiveness of salmeterol (50 microg)/ fluticasone propionate (100 microg) with that of oral montelukast (10mg) as initial maintenance therapy in patients with persistent asthma uncontrolled on short-acting beta2-agonist therapy alone.. A cost-effectiveness analysis was performed based on effectiveness and resource utilisation data that was prospectively collected from a randomised, double-blind, double-dummy, 12-week trial.. Patients (>15 years of age) who had asthma for at least 6 months. Effectiveness measurements in this analysis included improvement in forced expiratory volume in 1 second (FEV(1)) and symptom-free days (SFDs). Cost of asthma drug treatment as well as costs related to an asthma exacerbation were used in the cost analysis. The study assumed a payer's perspective. All costs are in 2001 US dollars.. Of the 423 patients eligible for the study, 211 were randomised to salmeterol/fluticasone propionate and 212 to montelukast. Treatment with salmeterol/fluticasone propionate resulted in a significantly higher proportion of patients who achieved a 12% increase in FEV(1) (successful treatment) [salmeterol/fluticasone propionate: 71% vs montelukast: 39%; p < 0.001] and percentage of SFDs (salmeterol/fluticasone propionate: 46.8% vs montelukast: 21.5%; p < 0.001) compared with montelukast. The mean daily costs per successfully treated patient were lower in the salmeterol/fluticasone propionate group (US dollars 5.03, 95% CI US dollars 4.61 to US dollars 5.50) compared with the montelukast group (US dollars 8.25, 95% CI US dollars 6.98 to US dollars 9.93). Furthermore, per patient mean daily cost per SFD was lower with salmeterol/fluticasone propionate (US dollars 7.63, 95% CI US dollars 6.90 to US dollars 8.50) compared with montelukast (US dollars 14.89, 95% CI US dollars 12.36 to US dollars 17.98). Incremental cost-effectiveness ratios (ICERs) showed that the additional costs to achieve these benefits with salmeterol/fluticasone propionate were minimal. With regards to improvement in lung function, the ICER was US dollars 1.33 (95% CI US dollars 0.80 to US dollars 2.02) and with regards to SFD, the ICER was US dollars 1.69 (95% CI US dollars 1.01 to US dollars 2.48). Sensitivity analysis demonstrated the stability of the results over a range of assumptions.. From a third-party payer perspective, this analysis shows that based on increased efficacy and only a slight increase in cost, twice-daily treatment with salmeterol/fluticasone propionate is more cost effective than once-daily treatment with montelukast as initial maintenance therapy for persistent asthma. This finding complements the results of the clinical analyses indicating that treatment of both inflammation and bronchoconstriction with products such as salmeterol/ fluticasone propionate may be more cost effective as initial maintenance asthma therapy than the use of leukotriene modifiers such as montelukast.

Topics: Acetates; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cost-Benefit Analysis; Cyclopropanes; Double-Blind Method; Drug Combinations; Female; Fluticasone; Humans; Male; Middle Aged; Quinolines; Salmeterol Xinafoate; Sulfides

Studies have shown fluticasone propionate (FP) 100, 200, and 500 microg administered once daily to be effective in the treatment of asthma. The efficacy of a once daily regimen of FP 250 microg has not been evaluated previously.. We sought to evaluate the efficacy and safety of inhaled FP 250 microg administered once daily in patients currently receiving inhaled short-acting beta-agonists (SABA) alone or inhaled corticosteroids (ICS).. In two separate studies, 408 patients in the SABA study and 401 patients in the ICS study were randomly assigned to receive FP 250 microg or placebo for 12 weeks through the Diskus device (GlaxoSmithKline, Research Triangle Park, NC) each morning.. At the study endpoint, SABA patients treated with FP and placebo had mean increases in forced expiratory volume in 1 second from baseline of 0.23 +/- 0.03 L and 0.10 +/- 0.03 L, respectively (P < 0.001). ICS patients treated with FP had a mean increase of 0.08 +/- 0.02 L compared with a decrease in forced expiratory volume in 1 second of -0.08 +/- 0.03 L with placebo (P < 0.001). Changes of similar magnitude in morning peak expiratory flow rates were seen with FP in both the SABA and ICS studies. Fewer FP-treated ICS study patients were withdrawn from the study as a result of predetermined asthma stability criteria and, therefore, those patients had a greater probability of remaining in the study than placebo-treated patients (P < 0.001).. FP 250 microg, once daily, produced greater improvements in pulmonary function and asthma symptom control than placebo. This new treatment regimen provides clinicians with an additional therapeutic option for patients with asthma previously treated with either beta2-agonists alone or ICS.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Treatment Outcome

Whether leukotriene receptor antagonists exhibit adequate anti-inflammatory effects in the treatment of asthma is still a controversial issue. The aim of the present study was to perform a direct comparison of the effects of a 4-week treatment with either montelukast (10 mg, once a day) or low-dose inhaled fluticasone (100 microg b.i.d.) on functional and inflammatory parameters in steroid-naïve patients with moderate asthma. Forty patients (forced expiratory volume in one second (FEV1), 60-80% predicted) were studied in a double-blind, randomised, crossover design. Treatment periods were separated by 3-8 weeks of washout. At the beginning and end of each period, FEV1, airway responsiveness to inhaled methacholine (provocative concentration causing a 20% fall in FEV1 (PC20)), the level of exhaled nitric oxide (NO) and sputum differential cell counts were determined. Only short-acting beta2-agonists were allowed for relief of symptoms. FEV1 increased by 0.50+/-0.07 L (mean+/-SEM) after fluticasone and by 0.37+/-0.07 L after montelukast (p<0.001, each), and PC20 by 1.33+/-0.13 (p<0.001) and 0.15+/-0.17 (NS) doubling doses, respectively. Correspondingly, percentages of sputum eosinophils were reduced by factor 2.7 (p<0.01) and 1.4 (nonsignificant (NS)), and the levels of exhaled NO (at 50 mL x s(-1)) by factor 2.1 (p<0.01) and 1.1 (NS). These data indicate a comparable bronchodilator action of montelukast and fluticasone in patients with moderate asthma, but additional attenuation of airway inflammation by fluticasone as detectable through noninvasive methods.

Topics: Acetates; Administration, Inhalation; Adolescent; Adult; Airway Resistance; Analysis of Variance; Androstadienes; Asthma; Bronchial Hyperreactivity; Cross-Over Studies; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Follow-Up Studies; Humans; Male; Middle Aged; Nitric Oxide; Probability; Quinolines; Reference Values; Respiratory Function Tests; Severity of Illness Index; Sputum; Sulfides; Treatment Outcome

Inhaled corticosteroids (ICS) are typically associated with a flat dose-response curve when traditional efficacy values are examined (eg, FEV(1)). The aim of the present study was to investigate if a dose-response relationship exists for lung function and inflammatory cell numbers in bronchial biopsy specimens.. Bronchial biopsy specimens were obtained from 36 patients randomized to receive 100 micro g, 500 microg, or 2,000 microg/d of fluticasone propionate (FP). Lung physiology and bronchial biopsies were performed at baseline and after 2 weeks of treatment.. Improvement in lung function and suppression of airway inflammation were optimal at a dose of 500 microg/d of FP. Significant changes from baseline following treatment were documented in FEV(1) (p = 0.02), forced expiratory flow (p = 0.002), FEV(1)/FVC (p = 0.007), provocative concentration of histamine causing a 20% fall in FEV(1) (PC(20)) [p = 0.02], T-cell numbers (p = 0.0005), activated eosinophils (p = 0.01), and numbers of macrophages (p = 0.01) in the group treated with 500 microg/d of FP. Comparison between groups administered different doses of FP failed to demonstrate a dose-response relationship for change from baseline in PC(20) (p = 0.43), any of the lung function parameters, T-cell numbers (p = 0.64), activated T cells (p = 0.46), eosinophils (p = 0.53), activated eosinophils (p = 0.48), or macrophage numbers (p = 0.68).. The apparent lack of a dose-response for ICS treatment in patients with asthma further validates the preferential use of add-on therapy over increasing the dose of ICS.

Topics: Adult; Androstadienes; Asthma; Biopsy; Bronchi; Dose-Response Relationship, Drug; Female; Fluticasone; Forced Expiratory Flow Rates; Forced Expiratory Volume; Humans; Lymphocyte Activation; Lymphocyte Count; Male; Middle Aged; T-Lymphocytes

Although the anti-inflammatory effects of inhaled corticosteroids in the treatment of asthma are established, the effects of long-acting beta2-adrenergic receptor agonists on inflammation are the subject of debate. The aim of the present study was to determine the effect of salmeterol on the numbers of inflammatory cells in biopsy samples of distinct immunophenotype and those expressing the genes for interleukin-4 and -5, regulatory cytokines particularly relevant to asthma. Twenty patients (aged 18-55 yrs) with mild stable asthma were randomised in a three-way crossover study to 6 weeks of treatment with: 1) salmeterol (50 microg b.d.; SM50); 2) fluticasone propionate (250 microg b.d.; FP250), or 3) placebo. Compared with placebo, SM50 significantly reduced the numbers of neutrophils in bronchial biopsy samples and the concentrations of myeloperoxidase and soluble E-selectin in serum, each of which reflect neutrophil involvement. Compared with FP250, SM50 reduced neutrophil number and human neutrophil lipocalin level in bronchial lavage fluid and intercellular adhesion molecule-1 level in bronchoalveolar lavage fluid. Compared with placebo, FP250 significantly reduced the numbers of (CD3+) T-lymphocytes, (CD4+) T-helper cells, (CD45RO+) activated T-helper cells and eosinophils in the biopsy samples; it also reduced the percentage of eosinophils and soluble intercellular adhesion molecule-1 in serum. The percentage of symptom-free days and nights and airways hyperresponsiveness improved significantly after SM50 compared to both placebo and FP250. In conclusion, a novel antineutrophilic effect of the inhaled long-acting beta2-adrenergic receptor agonist, salmeterol, in mild asthma is reported.

Topics: Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Biopsy; Bronchi; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Neutrophils; Salmeterol Xinafoate

In children with mild asthma, who show hardly any abnormalities in pulmonary function, objective measurement of the effect of inhaled corticosteroids is difficult. The short term effect of fluticasone propionate (FP) in these children was evaluated, using both subjective and objective parameters. A total of 68 children (5-10 yrs old) were randomly assigned to either FP 250 microg or placebo twice daily as metered-dose inhaler via spacer during 12 weeks. Symptom scores, use of rescue medication, wheezing, parent global evaluation and pulmonary function tests including forced expiratory volume in one second (FEV1), peak expiratory flow (PEF) and bronchial responsiveness (provocation dose of methacholine causing a 20% fall in FEV1 (PD20)) were evaluated. FP-treated versus placebo-treated children showed significant changes in percentage symptom-free days, use of beta2-mimetics, morning and evening PEF, FEV1 % pred and wheezing. No significant improvements were found in parent global evaluation, absolute values of FEV1 nor PD20. These findings show that inhaled corticosteroids are effective in children with mild asthma. This effect can be assessed by both objective and subjective parameters. Early start of inhaled corticosteroids should be considered even when pulmonary function is normal.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchial Provocation Tests; Bronchodilator Agents; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Humans; Male; Respiratory Function Tests

To assess effect of a breath-actuated inhaled steroid, Fluticasone Diskhaler (Flutide) on health-related quality of life in asthmatic patients using Hyland's living with asthma questionnaire (LWAQ).. Randomly selected asthmatic patients filled out the LWAQ (the first study). Then, the eight physicians switched inhaled steroid from pressurelized metered-dose inhaler of beclomethasone (BDI) to Flutide according to their own decision. Consequently some patients were switched their prescriptions and others were not. In 12 weeks after the first study, all the patients again filled out the LWAQ (the second study).. The patients treated with Flutide were 87 and without were 159. The scale scores of the Flutide group (mean, 1.900) were significantly higher than those of the BDI-group (mean, 1.789). In the second study, there was no significant difference between the scale scores in the two groups (mean, 1.782 vs. 1.705). Among the 8 domains, only medication score significantly decreased by Flutide therapy. More than 80% of the patients favored easy handling of Flutide including no necessity of the spacer.. Flutide therapy significantly improved quality of life in asthmatic patients. The possible mechanisms are the stronger effectiveness of fluticasone propionate and improvement of adherence to inhaled steroid.

Topics: Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Female; Fluticasone; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Patient Satisfaction; Quality of Life; Surveys and Questionnaires

Measurement of health-related quality of life (HR-QOL) may show benefits of asthma treatments not revealed by objective monitoring and can complement clinical and physiological assessments of treatment outcome. HR-QOL was measured in four countries in a multicenter, double-blind, randomized comparison of salmeterol/fluticasone propionate combination and budesonide in patients aged > or =12 years with moderate-to-severe asthma uncontrolled by inhaled corticosteroids.. Patients received, twice daily, either salmeterol/fluticasone propionate 50/250 microg (Seretide/ Advair) via Diskus inhaler (n = 55) or budesonide 800 microg (Pulmicort) via Turbuhaler (n = 58). Patients completed the Asthma Quality of Life Questionnaire (AQLQ) at baseline and after 12 weeks treatment (or early withdrawal). The analysis included 113 patients.. Mean improvement in AQLQ scores achieved clinical importance in all four domains in the salmeterol/fluticasone group (AQLQ change > or =0.5), but in only two domains in the budesonide group. Although the mean overall improvement in AQLQ scores observed in the salmeterol/fluticasone group was significantly greater than that observed in the budesonide group (difference of 0.45; p = 0.002), the difference was less than the minimal important difference (0.5). Nevertheless, further analysis showed that the number-needed-to-treat was only 3.4. This indicates that only 3.4 patients need to be treated with the salmeterol/fluticasone combination for one patient to experience a meaningful improvement in HR-QOL, relative to monotherapy with an increased dose of budesonide.. Treatment of moderate-to-severe asthma with salmeterol/fluticasone propionate resulted in superior gains in HR-QOL relative to increasing the dose of inhaled corticosteroids.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Combinations; Female; Fluticasone; Humans; Male; Middle Aged; Quality of Life; Salmeterol Xinafoate; Surveys and Questionnaires

Chronic controller therapy, particularly with inhaled corticosteroids, is required in patients with persistent bronchial asthma. Long-acting beta agonists provide prolonged bronchodilatation, improve symptoms and reduce exacerbations. A powder inhaler containing both fluticasone propionate and salmeterol xinafoate combines anti-inflammatory treatment and bronchodilatation in a single user-friendly device (Diskus).. The goal of the present study was to evaluate the efficacy and safety of salmeterol/ fluticasone (50/250 microg twice daily) as initial treatment for symptomatic patients with mild to moderate bronchial asthma who had not previously received appropriate anti-asthma medication.. This prospective study was conducted in 17 study centres located predominantly in private practices. 127 patients with mild to moderate asthma (FEV(1) >60% of predicted) aged 12 years and older were recruited into a one-week screening phase. If they used rescue medication on > or =3 of 7 days or had a total asthma symptom score of > or =5 points, they were admitted to the treatment phase and received salmeterol xinafoate (50 microg) and fluticasone propionate (250 microg) in a single dry powder inhaler (Diskus) for four weeks.. Combined salmeterol/fluticasone therapy improved morning and evening peak expiratory flow rates (PEFR) as measured by patients and reported in asthma diaries within the first week of treatment (by 35 and 28 L/min, respectively). At week 4, morning PEFR had increased by 57 L/min or 13.0 % predicted compared to baseline, and forced expiratory volume in one second (FEV1) had improved by 12.5% of predicted (p<0.001). Use of rescue medication declined by 1.9 puffs per day. Both patients and physicians regarded treatment as a major benefit: two thirds assessed treatment as "excellent". The combination was well tolerated.. The combined inhalation of salmeterol and fluticasone from a single dry powder inhaler (DiskuS) was an effective initial treatment for patients with mild to moderate asthma. Improvements of symptoms and lung function were documented by the first week of treatment. This combination provides rapid and effective asthma control that is highly acceptable to both the patient and physician.

Topics: Adolescent; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Drug Combinations; Drug Tolerance; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Prospective Studies; Safety; Salmeterol Xinafoate

Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is an accepted indicator of potential side effects from inhaled corticosteroids. Although cortisol monitoring is frequently used to detect changes in HPA axis activity, the optimal method for identifying the subset of asthma patients on inhaled steroids who experience severe cortisol suppression of potential clinical significance has not been established. The objective of this study was to compare several methods for assessing HPA axis activity in asthma patients taking inhaled corticosteroids. After screening, 153 patients with mild to moderate asthma were randomly assigned to receive inhaled fluticasone propionate (110, 220, 330, or 440 microg bid), flunisolide (500 microg or 1000 microg bid), or one of two control regimens (prednisone or placebo) for 21 days. Salivary (8 a.m.) and urinary (24-h) cortisol determinations were compared against 22-hour area under the serum cortisol concentration-time curve (AUC0-22 h) measured at baseline and on day 21. Comparisons were also made against 8 a.m. serum cortisol. A significant positive correlation was found between AUC0-22 h of serum cortisol and 8 a.m. serum cortisol level (r = 0.5140; p = 0.0001). The AUC0-22 h of serum cortisol was weakly correlated with 24-hour urinary cortisol levels, both corrected (r = 0.4388; p = 0.0001) and uncorrected (r = 0.3511; p = 0.0001) for creatinine excretion. The 8 a.m. salivary cortisol level correlated positively with the 8 a.m. serum cortisol level (r = 0.5460; p = 0.0001). Salivary cortisol was both sensitive and specific for the detection of a 50% decline in AUC0-22 h of serum cortisol. Cortisol reductions of this magnitude have been observed following repeated use of inhaled steroids. Because it is noninvasive, salivary cortisol measurement offers distinct advantages as a screening method for detecting pronounced HPA axis suppression in asthma patients receiving corticosteroid therapy.

Topics: Administration, Inhalation; Adrenocorticotropic Hormone; Adult; Analysis of Variance; Androstadienes; Anti-Inflammatory Agents; Area Under Curve; Asthma; Female; Fluocinolone Acetonide; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Nebulizers and Vaporizers; Patients; Pituitary-Adrenal System

Although inhaled corticosteroids have an established role in the treatment of asthma, studies have tended to concentrate on non-smokers and little is known about the possible effect of cigarette smoking on the efficacy of treatment with inhaled steroids in asthma. A study was undertaken to investigate the effect of active cigarette smoking on responses to treatment with inhaled corticosteroids in patients with mild asthma.. The effect of treatment with inhaled fluticasone propionate (1000 microg daily) or placebo for 3 weeks was studied in a double blind, prospective, randomised, placebo controlled study of 38 steroid naïve adult asthmatic patients (21 non-smokers). Efficacy was assessed using morning and evening peak expiratory flow (PEF) readings, spirometric parameters, bronchial hyperreactivity, and sputum eosinophil counts. Comparison was made between responses to treatment in non-smoking and smoking asthmatic patients.. There was a significantly greater increase in mean morning PEF in non-smokers than in smokers following inhaled fluticasone (27 l/min v -5 l/min). Non-smokers had a statistically significant increase in mean morning PEF (27 l/min), mean forced expiratory volume in 1 second (0.17 l), and geometric mean PC20 (2.6 doubling doses), and a significant decrease in the proportion of sputum eosinophils (-1.75%) after fluticasone compared with placebo. No significant changes were observed in the smoking asthmatic patients for any of these parameters.. Active cigarette smoking impairs the efficacy of short term inhaled corticosteroid treatment in mild asthma. This finding has important implications for the management of patients with mild asthma who smoke.

Topics: Administration, Inhalation; Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Double-Blind Method; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Peak Expiratory Flow Rate; Smoking; Sputum

Asthma is a chronic disease characterized by inflammation and bronchoconstriction. Medications that are able to effectively treat both components are advantageous.. To compare the efficacy of an inhaled corticosteroid and a long-acting beta2-agonist combination product with a leukotriene antagonist for initial maintenance therapy in patients who were symptomatic while receiving short-acting beta2-agonists alone.. A 12-week, randomized, double-blind, double-dummy, multicenter study was conducted in 432 patients 15 years of age and older with persistent asthma who were symptomatic on short-acting beta2-agonists alone. Fluticasone propionate 100 microg and salmeterol 50 microg combination product (FSC) twice daily or montelukast 10 mg once daily was administered.. At endpoint, compared with montelukast, FSC significantly increased morning predose forced expiratory volume in 1 second (0.61 +/- 0.03 L vs 0.32 +/- 0.03 L), morning peak expiratory flow rate (peak expiratory flow rate; 81.4 +/- 5.9 L/minute vs 41.9 +/- 4.8 L/minute), evening peak expiratory flow rate (64.6 +/- 5.3 L/minute vs 38.8 +/- 4.7 L/minute), the percentage of symptom-free days (40.3 +/- 2.9% vs 27.0 +/- 2.7%), the percentage of rescue-free days (53.4 +/- 2.8% vs 26.7 +/- 2.5%), and the percentage of nights with no awakenings (29.8 +/- 2.5% vs 19.6 +/- 2.1%) (P < or = 0.011, all comparisons). At endpoint, FSC significantly reduced asthma symptom scores (-1.0 +/- 0.1 vs -0.7 +/- 0.1) and rescue albuterol use (-3.6 +/- 0.2 puffs/day vs -2.2 +/- 0.2 puffs/day) compared with montelukast (P < 0.001). At endpoint, patients treated with FSC also had a significantly greater improvement in quality of life scores and were more satisfied with their treatment compared with montelukast-treated patients (P < or = 0.001). Both treatments were well tolerated.. Initial maintenance therapy with FSC provides greater improvement in asthma control and patient satisfaction than montelukast.

Topics: Acetates; Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Quinolines; Salmeterol Xinafoate; Sulfides

To study the systemic activity of inhaled steroids in young children.. Forty children with mild asthma aged 1 to 3 years were studied in a 3-way crossover, randomized, placebo-controlled, double-blind trial. Treatment with inhaled fluticasone propionate, 200 microg twice daily delivered via pressurized metered-dose inhaler (pMDI) and Babyhaler (FP400), was compared with budesonide, 200 microg twice daily delivered via pMDI and NebuChamber (BUD400), and to placebo. The Babyhaler was primed before use. Knemometry was used to detect systemic steroid activity. It was performed with a hand-held knemometer after 1 and 4 weeks of treatment. The increase in lower-leg length within this 3-week period was used as the outcome measure. The intention-to-treat population was analyzed by analysis of variance.. The increases in the lower-leg length during placebo, BUD400, and FP400 treatments were 85, 45, and 34 microm/d, respectively (adjusted mean). The growth in lower-leg length was significantly reduced from both steroid treatments. The difference between BUD400 and placebo was -40 microm/d (n = 25; 95% confidence interval [CI]: -8 to -72). The difference between FP400 and placebo was -51 microm/d (n = 26; 95% CI: -19 to -83). The difference between FP and BUD was -11 microm/d and was not statistically significant (n = 28; 95% CI: 20 to -42).. FP and BUD are both systemically active in children 1 to 3 years old when administered for 4 weeks from their dedicated spacer devices in daily doses of 400 microg with no difference between the 2 steroid regimens. These findings call for studies of clinical side effects from these treatments of preschool children.

Topics: Administration, Inhalation; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Child, Preschool; Cross-Over Studies; Double-Blind Method; Fluticasone; Growth; Humans; Infant; Leg; Nebulizers and Vaporizers

A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy.. The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs.. A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV(1) and PC(20); risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 microg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 microg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 microg/day.. Maximum FEV(1) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC(20) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV(1) response, in contrast to poor (<5%) response, was found to be associated with high exhaled nitric oxide (median, 17.6 vs 11.1 ppb), high bronchodilator reversibility (25.2% vs 8.8%), and a low FEV(1)/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC(20), in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years).. Near-maximal FEV(1) and PC(20) effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chronic Disease; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Methacholine Chloride; Middle Aged; Prospective Studies; Treatment Outcome

There are few data in asthma relating airway physiology, inflammation and remodelling and the relative effects of inhaled corticosteroid (ICS) treatment on these parameters. A study of the relationships between spirometric indices, airway inflammation, airway remodelling, and bronchial hyperreactivity (BHR) before and after treatment with high dose inhaled fluticasone propionate (FP 750 microg bd) was performed in a group of patients with relatively mild but symptomatic asthma.. A double blind, randomised, placebo controlled, parallel group study of inhaled FP was performed in 35 asthmatic patients. Bronchoalveolar lavage (BAL) and airway biopsy studies were carried out at baseline and after 3 and 12 months of treatment. Twenty two normal healthy non-asthmatic subjects acted as controls.. BAL fluid eosinophils, mast cells, and epithelial cells were significantly higher in asthmatic patients than in controls at baseline (p<0.01). Subepithelial reticular basement membrane (rbm) thickness was variable, but overall was increased in asthmatic patients compared with controls (p<0.01). Multiple regression analysis explained 40% of the variability in BHR, 21% related to rbm thickness, 11% to BAL epithelial cells, and 8% to BAL eosinophils. The longitudinal data corroborated the cross sectional model. Forced expiratory volume in 1 second improved after 3 months of treatment with FP with no further improvement at 12 months. PD(20) improved throughout the study. BAL inflammatory cells decreased following 3 months of treatment with no further improvement at 12 months (p<0.05 v placebo). Rbm thickness decreased in the FP group, but only after 12 months of treatment (mean change -1.9, 95% CI -3 to -0.7 microm; p<0.01 v. baseline, p<0.05 v. placebo). A third of the improvement in BHR with FP was associated with early changes in inflammation, but the more progressive and larger improvement was associated with the later improvement in airway remodelling.. Physiology, airway inflammation and remodelling in asthma are interrelated and improve with ICS. Changes are not temporally concordant, with prolonged treatment necessary for maximal benefit in remodelling and PD(20). Determining the appropriate dose of inhaled steroids only by reference to symptoms and lung function, as specified in current international guidelines, and even against indices of inflammation may be over simplistic. The results of this study support the need for early and long term intervention with ICS, even in patients with relatively mild asthma.

Topics: Administration, Topical; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Basement Membrane; Biopsy; Bronchial Hyperreactivity; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Bronchoscopy; Collagen; Cross-Sectional Studies; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Longitudinal Studies; Mast Cells; Middle Aged; Observer Variation; Regression Analysis

Asthma is a chronic-episodic disease characterised by acute, symptomatic episodes of varying severity. We developed a Markov model that can be used to estimate the cost effectiveness of alternative asthma treatments. Because of the costs they incur, asthma exacerbations ('attacks') requiring intervention by a healthcare professional were a central consideration in the development of the model.. Treatment success was assessed as asthma control, a composite measure based on goals defined in world-wide asthma management guidelines and in terms of quality-adjusted life-years (QALYs). The data from which the transition probabilities were derived came from patients with asthma who received either salmeterol/fluticasone propionate combination (SFC) 50/100microg or fluticasone propionate (FP) 100microg, administered twice daily via an inhaler, in a 12-week, randomised, double-blind, clinical trial. Costs were estimated from resource profiles defined for each of the model states. A key aspect of the model was the use of probabilistic sensitivity analysis techniques to examine the uncertainty in the cost-effectiveness results. Distributions were fitted to transition probabilities and to cost input parameters and values were sampled at random from these distributions using a second order Monte Carlo simulation technique. This produced a distribution for incremental cost effectiveness that was employed to construct 95% uncertainty intervals and to construct cost effectiveness acceptability curves.. In this analysis, the model was run over a 12-week period using transition probabilities derived from the trial data. The results showed that treatment with SFC resulted in a higher proportion of successfully controlled weeks per patient than treatment with FP (66 vs 47%), and higher mean weekly direct asthma management costs (pound sterling 15.77 vs pound sterling 11.83; 2000 values). The average incremental cost per successfully controlled week with SFC was pound sterling 20.83. Probabilistic sensitivity analysis showed that the 95% uncertainty intervals for the incremental cost-effectiveness ratio was - pound sterling 64.94 to pound sterling 112.66. In approximately 25% of cases, SFC was dominant (more effective and less costly), but in the remaining cases, it was both more effective and more costly. It was shown that if decision makers are willing to pay approximately pound sterling 45 for an additional successfully controlled week, SFC will be the more cost-effective strategy in this patient population for 80% of the time.. This is one of the first decision-analytic models of asthma to incorporate probabilistic sensitivity analysis techniques to explore uncertainty. The model's flexible yet standardised framework permits the cost effectiveness of alternative asthma management strategies in different healthcare settings to be established.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child, Preschool; Cost-Benefit Analysis; Double-Blind Method; Female; Fluticasone; Humans; Male; Markov Chains; Middle Aged; Models, Economic; Quality-Adjusted Life Years; Treatment Failure

The optimal inhalation flow of dry powder formula fluticasone dipropionate (DFP) is not known. This study investigated the clinical effects of inhaling a flow of DFP. A randomized cross-over trial was applied to 13 patients with chronic persistent asthma. After a 2-week run-in period using the current dose of beclomethasone from a metered dose inhaler (BDP-run), BDP was replaced with an equipotent amount of DFP. The patients entered either an 8-week run with high-flow (> 100 L/min) inhalation followed by a 4-week run with medium-flow (70 L/min) (HM group) or a medium-flow run followed by a high-flow run (MH group). The peak inhaling flow from DFP was measured daily. The mean of the inhalation flow in the high-flow run (111.4 +/- 3.6 (SE) L/min) was significantly higher than that (77.3 +/- 0.6 L/min) in the medium-flow run. In both groups, morning and evening peak expiratory flows (PEFs) increased in the first week of change from BDP to DFP, peaking in the first 8-week run, then maintained this level until the end of the following 4-week run. When PEFs in the last week of the 3 runs were compared, those during the DFP-run of either flow were significantly larger than those during the BDP-run, but the PEFs during the high-flow and medium-flow runs were not significantly different. The asthma symptoms also improved with a change from BDP to DFP, but the symptoms did not change with a change in the inhalation flow rate. An inhaled flow of up to 111 L/min is acceptable in terms of clinical efficacy for the use of DFP.

Topics: Administration, Inhalation; Adult; Aged; Androstadienes; Asthma; Bronchodilator Agents; Chronic Disease; Female; Fluticasone; Humans; Male; Middle Aged; Nebulizers and Vaporizers

To compare clinical, device and biochemical aspects of monotherapy with flixotide vs combination of flixotide with serevent in patients with moderate bronchial asthma (MBA).. 18 patients with MBA received flixotide and 18 MBA patients flixotide plus serevent for two weeks of lead-in and eight weeks of basic treatment. A special study was made of neutrophils which were examined for activity of LPO-antioxidants and phospholipid spectrum of membranes.. There were similar changes in function of the system LPO-antioxidants and lipid structure in neutrophilic membranes of moderate BA patients of both the groups.. Clinicobiochemical efficacy of mean doses of a new topic inhalation glucocorticoid flixotide alone or in combination with prolonged beta 2-adrenostimulator serevent is demonstrated. There were positive trends in metabolic processes in neurophilic membrane. Use of flixotide in combination with serevent is clinically preferable.

Topics: Adrenergic beta-Agonists; Adult; Albuterol; alpha-Tocopherol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Catalase; Drug Therapy, Combination; Female; Fluticasone; Glutathione Reductase; Humans; Lipid Peroxidation; Male; Malondialdehyde; Phospholipids; Receptors, Adrenergic, beta-2; Salmeterol Xinafoate; Schiff Bases; Superoxide Dismutase

The level of exhaled nitric oxide (FENO) is increased in house dust mite (HDM)-sensitized asthmatic children after exposure to HDM antigen, and inhaled steroids can prevent this increase. The aim of this study was to evaluate whether montelukast could prevent an increase in FENO levels in allergic asthmatic children after a brief period of exposure to relevant allergens. Sixteen children were evaluated at the residential house 'Istituto Pio XII' (Misurina, Bellunio, Italy) in the Italian Alps, a dust mite-free environment. FENO levels were evaluated before (t0) and immediately after (t1) the children were exposed to HDM allergens for 2 weeks in their homes at sea level. No significant difference in FENO was observed in the fluticasone-treated group of children after 2 weeks at sea level. In the group treated with montelukast, an increase in FENO was observed between t0 and t1, which failed to reach statistical significance. These preliminary data suggest that oral montelukast could be effective in preventing the relapse in airway inflammation in allergic asthmatic children who are occasionally exposed to relevant allergens for a short period of time.

Topics: Acetates; Adolescent; Allergens; Androstadienes; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Breath Tests; Child; Cyclopropanes; Dust; Fluticasone; Humans; Leukotriene Antagonists; Mites; Nitric Oxide; Quinolines; Respiratory Function Tests; Respiratory Hypersensitivity; Sulfides; Treatment Outcome

In the treatment of asthma, inhaled steroids are more effective than cromolyn, whereas the latter offers extreme safety. The aim of the present pilot study was to evaluate, contemporarily, efficacy and safety aspects of different asthma treatment modalities. In 75 school-age children (mean age 9.5 years; range 5.5-14.7 years), treatment of asthma was started with budesonide (BUD, n = 30), fluticasone propionate (FP, n = 30) or cromones (CROM, n = 15). BUD was used at a dose of 800 microg/day during the first 2 months and at 400 microg/day thereafter. The respective FP doses were 500 and 200 microg/day. Efficacy of the treatment was assessed by measuring forced expiratory volume in 1 second (FEV1) and by evaluating the use of bronchodilators. Side-effects of the treatment were evaluated by following growth of the children and by performing low-dose adrenocorticotropin (ACTH) testing. At 4 months FEV1 had improved by a mean of 8.2% in the BUD group and by 5.4% in the FP group (p< 0.01 vs. baseline in both groups; NS between BUD and FP groups). The use of bronchodilators had decreased from five doses/week to one dose/week in the BUD group (p< 0.05), and from three doses/week to one dose/week in the FP group (p< 0.01) (NS between the groups). In the CROM group, the FEV1 value and the use of bronchodilators did not change. The treatment was unsuccessful on the basis of FEV1 decrease and increased bronchodilator use in, respectively, 30 and 15% of the BUD-, 20 and 7% of the FP-, and 50 and 47% of the CROM-treated children. Therefore, to prevent one treatment failure in the CROM group, between three and five children would need to move to treatment with steroids. The treatment had measurable systemic effects on the basis of height standard deviation (SD) score decrease and minor adrenocortical suppression in, respectively, 60 and 30% of the BUD-, 27 and 17% of the FP-, and 20 and 0% of the CROM-treated children. Therefore, to avoid systemic effects in one steroid-treated child, three BUD- and six to 14 FP-treated children would need to move to treatment with CROM. In conclusion, in school-age children asthma should be treated first with inhaled steroids. It is probable that the best combination of efficacy and safety can be achieved by using low steroid doses.

Topics: Administration, Inhalation; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Child; Cromolyn Sodium; Dose-Response Relationship, Drug; Fluticasone; Forced Expiratory Volume; Humans; Pilot Projects; Treatment Outcome

To compare the long-term effects of an inhaled corticosteroid with those of a leukotriene modifier on measures of clinical efficacy, subject preference, and safety in patients with persistent asthma.. Between November 17, 1998, and May 26, 2000, we conducted a multicenter, randomized, double-blind, double-dummy, parallel-group study of patients aged 15 years or older with persistent asthma. The patients were symptomatic while taking short-acting beta2-agonists alone and were treated with fluticasone propionate (88 microg [2 puffs of 44 microg] twice daily) or montelukast (10 mg/d) for 24 weeks. Measures of pulmonary function, asthma symptoms, albuterol use, nighttime awakenings, physician assessments of efficacy, patient satisfaction, asthma-related quality of life, and safety were evaluated.. A total of 522 patients were randomized to receive fluticasone or montelukast, and 395 patients completed the study. At end point, treatment with fluticasone significantly improved pulmonary function, asthma symptom scores, the percentage of symptom-free days, rescue albuterol use, and the number of nighttime awakenings due to asthma when compared with montelukast (P< or = .002, each comparison). Significantly more patients were satisfied with fluticasone therapy (83%) compared with montelukast therapy (66%) (P<.001), and fluticasone therapy was rated as effective by a significantly greater portion of physicians (67%) than was montelukast therapy (54%) (P<.001). Treatment with fluticasone significantly improved asthma-related quality-of-life measures compared with montelukast (P< or =.01). The incidence of asthma exacerbations was similar in the fluticasone (19 patients, 7%) and montelukast (21 patients, 8%) treatment groups, although slightly more patients in the montelukast group were withdrawn from the study because of asthma exacerbations (6% vs 4%, respectively).. Long-term treatment with a low dose of inhaled fluticasone is more effective than oral montelukast as first-line maintenance therapy for the treatment of persistent asthma.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Chronic Disease; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Headache; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Patient Satisfaction; Quality of Life; Quinolines; Respiratory Tract Infections; Sleep Initiation and Maintenance Disorders; Sulfides; Treatment Outcome

Although corticosteroid therapy for asthma improves lung function and reduces airway inflammation, the relation between these two events is unclear. This article investigates associations between changes in bronchial inflammation and lung function during high-dose inhaled corticosteroid therapy for asthma.. Nine subjects with atopic asthma received high-dose inhaled fluticasone propionate (FP), 2,000 microg/d for 8 weeks. Fiberoptic bronchoscopy with endobronchial biopsies, spirometry, and histamine provocation challenge were performed on each subject at baseline, after 2 weeks, and again after 8 weeks of therapy. Spearman rank correlation coefficients between changes in parameters of bronchial inflammation and lung function were computed.. As expected, significant down-regulation of airway inflammation and improvements in lung function were observed after both short-term and long-term therapy with high-dose inhaled FP. During corticosteroid therapy, changes in lymphocyte and macrophage numbers in bronchial biopsy specimens were closely correlated. Changes in EG1+ eosinophils were associated with changes in EG2+ eosinophils after 8 weeks of therapy. Although changes in airway inflammation and changes in lung function were not closely associated after 2 weeks of therapy, changes in eosinophils (EG1) in bronchial biopsy specimens correlated with changes in bronchodilator response (r = 0.77, p = 0.016) after 8 weeks of therapy.. In patients with atopic asthma, changes in bronchial eosinophils and lung function during steroid therapy are closely related but do not occur simultaneously.

Topics: Administration, Inhalation; Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Biopsy; Bronchi; Bronchial Provocation Tests; Bronchodilator Agents; Bronchoscopy; Cell Count; Double-Blind Method; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Histamine; Humans; Hypersensitivity, Immediate; Inflammation; Lymphocytes; Macrophages; Male; Middle Aged; Skin Tests; Spirometry

The goal of this study was to establish a reliable method to evaluate systemic bioavailability and to determine equisystemic effects (microgram dose producing equal systemic cortisol suppression) of inhaled corticosteroids (ICS). Steroid naive asthma subjects (n = 156) were enrolled at six centers. A 1-week doubling dose design was used for each of six ICS and matched placebos for a total of four doses. Systemic effect was evaluated by hourly plasma cortisol concentrations (8 P.M. to 8 A.M.), 12- and 24-hour urine cortisol concentrations, and a morning blood osteocalcin. The area under the concentration-time curve for hourly cortisol concentrations was the best outcome variable to assess systemic effect. For the six ICS and matching placebos (beclomethasone-chlorofluorocarbon [CFC], budesonide dry powder inhaler [DPI], fluticasone DPI, fluticasone-CFC metered dose inhaler [MDI], flunisolide-CFC, and triamcinolone-CFC), only the placebo group and fluticasone DPI did not demonstrate a significant dose-response effect. Thus microgram comparison of all ICS could only be performed at a 10% cortisol suppression: flunisolide-CFC - 936; triamcinolone-CFC - 787; beclomethasone-CFC - 548; fluticasone DPI - 445; budesonide DPI - 268; fluticasone-CFC MDI - 111. This study represents the first step in evaluation of ICS efficacy based on equisystemic (cortisol suppression) effects of a given ICS, rather than doses judged arbitrarily to be comparable on a microgram basis.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Asthma; Beclomethasone; Budesonide; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluocinolone Acetonide; Fluticasone; Follow-Up Studies; Humans; Hydrocortisone; Male; Middle Aged; Probability; Reference Values; Single-Blind Method; Treatment Outcome; Triamcinolone

Inhaled glucocorticosteroids may reduce airway mucosal oedema in acute asthma. Inhaled platelet-activating factor (PAF) provokes pulmonary gas exchange disturbances, similar to those shown in severe asthma, which may be due to increased airway plasma leakage. This randomized, double-blind, placebo-controlled, crossover study investigated the effects of high doses of inhaled fluticasone propionate (FP) in 12 patients with mild asthma before and after PAF inhalation. Patients were studied before and 12 h after inhaling FP (6 mg) or placebo (P), and then at 5, 15 and 45 min after PAF challenge. Compared with vehicle, FP inhaled before PAF improved forced expiratory volume in one second and respiratory system resistance (Rrs), increased peripheral blood neutrophils and reduced eosinophil counts. After PAF, FP enhanced transient neutropenia at 5 min and facilitated the recovery of oxygen tension in arterial blood (FP: 93+/-4 mmHg; P: 83+/-4 mmHg) at 45 min, without influencing the increases in Rrs. In conclusion, the improvement of platelet-activated factor-induced oxygen tension in arterial blood disturbances after fluticasone proprionate suggests that inhaled glucocorticosteroids may possess vasoconstrictor properties in the pulmonary circulation.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Blood Gas Analysis; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Drug Interactions; Female; Fluticasone; Humans; Male; Platelet Activating Factor; Pulmonary Gas Exchange; Pulmonary Ventilation; Respiratory Mucosa; Time Factors; Treatment Outcome

Options for step-down therapy include use of inhaled corticosteroids alone or in combination with a long-acting beta2-agonist.. We sought to evaluate step-down therapy with a fluticasone propionate-salmeterol (FP-SM) combination administered through a dry powder inhaler (DPI; Advair Diskus) versus a medium dose of hydrofluoroalkane 143a-beclomethasone dipropionate (HFA-BDP) administered through a breath-actuated pressurized metered-dose inhaler (QVAR Autohaler).. Thirty-nine patients with uncontrolled moderate-to-severe asthma were treated with 1000 microg of DPI-administered BDP twice daily (DPI-BDP) for 4 weeks and then randomized to 200 microg of HFA-BDP twice daily (n = 20) or 100 microg of FP and 50 microg of SM twice daily (FM-SM; n = 19) for 8 weeks in a double-blind, double-dummy, parallel-group design. We measured the provocative dose of methacholine producing a 20% fall in FEV1 (methacholine PD20) as the primary outcome, with secondary outcomes being lung function, surrogate inflammatory markers, diary card responses, quality of life, and safety.. There was a 0.9 (95% confidence interval, 0.5-1.2) doubling dose improvement in methacholine PD20 comparing asthma before versus after DPI-BDP. HFA-BDP maintained this improvement, whereas FP-SM produced a further significant improvement, amounting to a 1.1 (95% confidence interval, 0.2-2.1) doubling dose difference at 8 weeks for FP-SM versus HFA-BDP. Effects on FEV1, peak expiratory flow, and quality of life (symptoms and emotions) were similar to those on methacholine PD20, with a significant difference between FP-SM and HFA-BDP. Suppression of plasma and urinary cortisol and serum osteocalcin levels occurred with DPI-BDP, but values returned to baseline levels within 1 month of HFA-BDP or FP-SM administration.. After high-dose inhaled corticosteroid, stepping down with the combination inhaler conferred further improvements in bronchoprotection, bronchodilatation, and clinical control, but not inflammatory markers, compared with that seen with a medium dose of inhaled corticosteroid.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchodilator Agents; Drug Administration Schedule; Drug Therapy, Combination; Fluticasone; Humans; Hydrocarbons, Fluorinated; Middle Aged; Outcome Assessment, Health Care; Quality of Life; Respiratory Function Tests; Salmeterol Xinafoate

To compare the efficacy and safety of fluticasone propionate and zafirlukast in patients with relatively stable persistent asthma who were previously treated with inhaled corticosteroids and short-acting beta(2)-agonists.A total of 440 patients (> or =12 years of age) previously treated with inhaled corticosteroids (beclomethasone dipropionate or triamcinolone acetonide) and short-acting beta(2)-agonists were included in this randomized double-blind study. After an 8-day run-in period, patients were treated with fluticasone (88 microg) or zafirlukast (20 mg) twice daily for 6 weeks. Outcome measures included pulmonary function (forced expiratory volume in 1 second [FEV(1)], peak expiratory flow [peak flow]), albuterol use, asthma symptoms, withdrawals due to lack of efficacy, and asthma exacerbations. Patients treated with fluticasone (n = 224) experienced greater mean increases in FEV(1) (0.24 L vs. 0.08 L, P <0.001), morning peak flow (30 L/min vs. 6 L/min, P <0.001), and evening peak flow (23 L/min vs. 5 L/min, P <0.001) during the study than did those treated with zafirlukast (n = 216). Fluticasone-treated patients had significantly greater increases in the mean percentages of symptom-free days (22% vs. 8%, P <0.001), rescue-free days (23% vs. 10%, P = 0.002), nights with uninterrupted sleep (<1% vs. -5%, P = 0.006), and fewer asthma exacerbations (1% vs. 6%, P = 0.005). Fewer fluticasone-treated patients were withdrawn due to lack of efficacy (2% vs. 13%, P <0.001).Inhaled fluticasone was more effective than zafirlukast in maintaining or improving asthma control in patients with relatively stable asthma who were switched from low-dose inhaled corticosteroids.

Topics: Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Double-Blind Method; Female; Fluticasone; Humans; Indoles; Male; Phenylcarbamates; Respiratory Function Tests; Sulfonamides; Tosyl Compounds; Treatment Outcome

To observe the efficacy of Fluticasone inhalation combined with Jinacon (JNC) orally taken in treating patients of chronic asthma (CA) of moderate degree.. Seventy-two CA patients were divided into three groups randomly and treated with Fluticasone inhalation combined with JNC, Fluticasone inhalation alone and JNC alone respectively for 4 weeks. The changes of clinical symptoms, airway reactivity and pulmonary function after treatment were observed.. The clinical symptoms, pulmonary function and airway hyper-reactivity were improved in all the three groups after treatment (P < 0.05 or P < 0.01), but the improvement was more significant in the group treated with the combined therapy (P < 0.05 or P < 0.01).. Fluticasone inhalation combined with JNC orally taken is an effective therapy in treating patients of chronic asthma of moderate degree.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Fluticasone; Ginkgo biloba; Humans; Male; Middle Aged; Phytotherapy

Combinations of inhaled glucocorticoids and long-acting beta2-agonists in the same inhaler device have become available in recent years. In this double-blind, randomized, placebo-controlled and crossover study we have evaluated the onset of action of budesonide and formoterol in a single inhaler (Symbicort Turbuhaler) and that of the fixed combination of salmeterol and fluticasone (Seretide Diskus). Thirty patients with a mean FEV1 of 2.54 l (range: 1.48-4.28) and a mean inclusion reversibility in FEV1 of 19.1% were included. Single doses of budesonide/formoterol 160/4.5 microg and 2x (160/4.5) microg, salmeterol/fluticasone 50/250 microg, or placebo were given. Serial measurements of FEV1 were performed over 3 h. The combination of one or two inhalations of budesonide/formoterol showed a faster onset of action than salmeterol/fluticasone, both evaluated as mean FEV1 at 3 min (2.74, 2.75 and 2.56 l respectively P<0.001 for both doses of budesonide/formoterol), or as average FEV1 from 0 to 15 min (2.80, 2.83 and 2.67 l respectively P<0.001 for both doses of budesonide/formoterol). For placebo, mean FEV1 at 3 min was 2.46 l, and the average FEV1 at 0-15 min was 2.50 l. Furthermore, budesonide/formoterol at both doses resulted in higher FEV1 than salmeterol/fluticasone at 3 h. We conclude that the combination of budesonide/formoterol has a faster onset of action than salmeterol/fluticasone.

Topics: Administration, Inhalation; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Salmeterol Xinafoate; Spirometry; Treatment Outcome

The potential for long term adverse effects from inhaled corticosteroids relates to their systemic absorption, usually assessed from proxy markers in short term studies. When fluticasone propionate and budesonide have been compared in this way the results have been inconsistent. To determine whether this is because of the subjects studied or the sensitivity of the systemic marker used, we have compared the effects of fluticasone propionate and budesonide in healthy and asthmatic subjects and investigated the effect of treatment on three systemic markers.. Forty six healthy subjects were randomised to receive inhaled fluticasone propionate 1500 microg/day (via an Accuhaler), budesonide 1600 microg/day (via a Turbuhaler), or placebo; 31 subjects with moderately severe asthma were randomised to receive the same doses of fluticasone propionate or budesonide but not placebo. Systemic effects in healthy and asthmatic subjects were compared after 7 days. Treatment was continued for another 21 days in the subjects with asthma when systemic effects and asthma control were assessed.. At baseline healthy subjects had higher urinary levels of total cortisol metabolites (TCM) than subjects with asthma. After 7 days of treatment with fluticasone propionate urinary TCM levels in the healthy subjects were significantly lower than in the subjects with asthma (mean difference between groups 1663 microg/day, 95% CI 328 to 2938). This was not the case with budesonide, however, where urinary TCM levels in the healthy subjects remained above those in the asthmatic subjects (mean difference between groups 1210 microg/day, 95% CI -484 to 2904). Urinary TCM levels were considerably more sensitive to the effects of inhaled corticosteroids than morning serum cortisol or osteocalcin concentrations. Only budesonide reduced the serum level of osteocalcin.. When given by dry powder inhaler for 7 days, fluticasone propionate 1500 microg/day has a greater effect on the hypothalamic-pituitary-adrenal axis in healthy subjects than in subjects with asthma, but this is not the case for budesonide 1600 microg/day. These findings, together with the differences in sensitivity between systemic markers, explain many of the discrepancies in the literature.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Powders

This multi-centre, randomized, double-blind, double-dummy, parallel-group study was designed to investigate the hypothesis of equivalent efficacy and comparable safety of two inhaled presentations of salmeterol/fluticasone propionate combination product (SALM/FP) 50/100 microg administered twice daily to patients with mild-to-moderate asthma for 12 weeks. The delivery systems were a 25/50 microg strength hydrofluoroalkane (HFA) metered-dose inhaler (MDI) and a Diskus inhaler (50/100 microg strength). A third group received FP 100 microg twice daily via a chlorofluorocarbon MDI (50 microg strength). A total of 497 patients aged 11-79 years with reversible airways obstruction who were symptomatic on inhaled corticosteroid (ICS) therapy and had room for improvement in lung function were randomized to treatment in a double-blind, parallel-group design (SALM/FP MDI: n=165; SALM/FP Diskus: n=167; FP MDI: n=165) for 12 weeks. A total of 383 patients completed the study according to the protocol. According to the primary efficacy variable, increase in mean morning PEF over weeks 1-12, the two inhaled presentations of SALM/FP were clinically equivalent (adjusted mean increases 43 and 46 l min(-1); treatment difference 3 l min(-1); 95% confidence interval: -6 to 11 l min(-1)). Equivalence was also demonstrated by all secondary efficacy measures. The SALM/FP MDI was significantly superior to the FP MDI for increase in mean morning PEF (treatment difference 19 l min(-1); P<0.001) and for all secondary measures except FEV1 and symptom-free nights. There was no significant difference between the groups with respect to adverse events and serum cortisol levels. These results demonstrate that the SALM/FP 25/50 microg HFA MDI (two inhalations twice daily) is clinically equivalent to the SALM/FP 50/100 microg Diskus (one inhalation twice daily). Patients switching to SALM/FP from other MDI-based asthma treatments may now do so without a change of delivery device.

Topics: Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Asthma; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Drug Therapy, Combination; Female; Fluticasone; Follow-Up Studies; Humans; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Therapeutic Equivalency; Treatment Outcome

Both inhaled corticosteroids and leukotriene modifiers are used in the maintenance treatment of persistent asthma.. The goal was to compare the efficacy and safety of low-dose fluticasone propionate (FP) and montelukast as first-line maintenance therapy in symptomatic patients by using short-acting beta2-agonists alone to treat persistent asthma.. In this multicenter, randomized, double-blind, double-dummy, parallel-group study, 533 patients (>15 years old) with persistent asthma who remained symptomatic while taking short-acting beta2-agonists alone were treated with FP (88 microg [2 puffs of 44 microg] twice daily) or montelukast (10 mg once daily) for 24 weeks.. Compared with treatment with montelukast, treatment with FP resulted in significantly greater improvements at endpoint in morning predose FEV(1) (22.9% vs 14.5%, P <.001), forced midexpiratory flow (0.66 vs 0.41 L/sec, P <.001), forced vital capacity (0.42 vs 0.29 L, P =.002), morning peak expiratory flow (PEF) (68.5 vs 34.1 L/min, P <.001), and evening PEF (53.9 vs 28.7 L/min, P <.001). Similar improvements in PEF were observed in patients with milder asthma (>70%-80% predicted FEV(1)). At endpoint, FP was more effective than montelukast at decreasing rescue albuterol use (3.1 puffs/day vs 2.3 puffs/day, P <.001), asthma symptom scores (-0.85 [48.6% decrease] vs -0.60 [30.5%], P <.001), and nighttime awakenings due to asthma (-0.64 awakenings/night [62% decrease] vs -0.48 awakenings/night [47.5%], P =.023), and FP increased the percentage of symptom-free days (32.0% vs 18.4% of days, P <.001) compared with montelukast. The adverse event and asthma exacerbation profiles for FP and montelukast were similar.. Low-dose FP is more effective than montelukast as first-line maintenance therapy for patients with persistent asthma who are undertreated and remain symptomatic while taking short-acting beta2-agonists alone.

Topics: Acetates; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Cyclopropanes; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; Male; Middle Aged; Quinolines; Sulfides

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Prednisone

Hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) extra-fine aerosol and HFA-fluticasone propionate (HFA-FP) are chlorofluorocarbon-free inhalers. We conducted an 8-week, open study to demonstrate the equivalence of HFA-BDP (800 microg day(-1)) and HFA-FP (1000 microg day(-1)) in moderate to severe asthma. Symptomatic patients on 500-1000 microg day(-1) CFC-BDP (or equivalent) and short-acting beta-agonist, were randomized to HFA-BDP (n = 101) or HFA-FP (n = 97) after 7-14 (+/-2) day run-in. In the intent-to-treat (ITT) population (n = 198), both treatments provided clinically and statistically significant improvements in asthma control, with increases in peak expiratory flow in the morning (AM PEF) and asthma symptoms (within treatment analysis P<0.05). Mean (SE) change in AM PEF from baseline at week 8 was equivalent (defined as 90% CI for the mean difference between treatments within +/-25 l min(-1)) in the two groups: 29.59 (5.19) l min(-1) for HFA-BDP vs. 17.3 (5.45) l min(-1) for HFA-FP (90% CI-0.02, 24.91). For the perprotocol population (n = 121), the mean (SE) change in AM PEF from baseline was not equivalent; AM PEF improved to a significantly greater extent in the HFA-BDP group than HFA-FP group [34.84 (7.08) vs. 20.63 (7.32) l min(-1) P<0.01; 90% CI; 2.66, 31.10]. At week 8 in the ITT population, there were no statistically significant differences in FEV1, beta-agonist use, asthma symptom/sleep disturbance scores, or percentage of days without asthma symptoms/sleep disturbance. There was a significantly greater reduction from baseline in mean eosinophil count for HFA-BDP compared with HFA-FP at weeks 3 and 8 (P<0.01), and eosinophil cationic protein value at week 8 (P<0.01). Both treatments were well tolerated and there were no statistically significant differences in urinary cortisol creatinine parameters. In conclusion, this study showed that, in patients with moderate-to-severe symptomatic asthma, HFA-BDP extra-fine aerosol 800 microg(-1) was at least as effective and equally well tolerated as 1000 microg day(-1) HFA-FP.

Topics: Adolescent; Adult; Aerosol Propellants; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Eosinophils; Equipment Design; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Leukocyte Count; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Treatment Outcome

An observational study using pharmacy and medical claims was used to determine whether there are differences in asthma care cost between patients that are newly started on montelukast and low-dose fluticasone propionate. Patients were identified who had at least one ICD-9 (493.XX) claim for asthma and were newly prescribed inhaled fluticasone propionate 44 microg (FP) or montelukast 5 or 10 mg (MON). Subjects could not have had a claim for any inhaled corticosteroid or oral leukotriene modifier in 9 months prior to the first prescription claim for either FP or MON. They were subsequently followed for 9 months. Multi-variate regression analysis was used to determine the influence of these single-controller therapies on post-index asthma related costs. Positively skewed cost variables were log-transformed prior to their inclusion into the multi-variate model. Asthma-related costs were adjusted for age, gender, health plan, co-morbidities, pre-index asthma medication use and pre-index asthma care costs. Multivariate regression analysis, adjusting for baseline covariates, indicated that compared to treatment with montelukast, treatment with FP had significantly (P<0.001) lower post-index total asthma related costs. Adjusted least squares mean total asthma care costs for the 9-month post-index period were $US649 for FP 44 microg compared to $US1028 for montelukast.

Topics: Acetates; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Cyclopropanes; Female; Fluticasone; Health Care Costs; Humans; Linear Models; Logistic Models; Male; Middle Aged; Quinolines; Regression Analysis; Retrospective Studies; Statistics, Nonparametric; Sulfides

Adding salmeterol to low-dose fluticasone propionate (FP) produces greater improvements in pulmonary function and symptom control than increasing the dose of FP in patients who remain symptomatic with low-dose FP.. We sought to compare the rates and characteristics of asthma exacerbations in patients after adding salmeterol to low-dose FP with the rates and characteristics of exacerbations in patients receiving higher dose FP.. In 2 multicenter, double-blind studies, 925 patients 12 years of age and older receiving 88 microg twice daily FP randomly received either 42 microg of salmeterol and 88 microg of FP or an increased dose of FP (220 microg) twice daily for 24 weeks. Exacerbation rates and clinical measures of asthma worsening were assessed for all patients who experienced an asthma exacerbation.. The addition of salmeterol resulted in a significantly lower rate and number of exacerbations compared with higher dose FP. A total of 41 (8.8%) patients experienced 47 exacerbations with the addition of salmeterol compared with 63 (13.8%) patients with 75 exacerbations in the group receiving increased-dose FP (P =.017). Salmeterol plus low-dose FP was significantly more protective than increased-dose FP in preventing asthma exacerbations, as assessed by the time to first exacerbation (P <.05). In both groups clinical indicators of worsening asthma showed parallel changes before asthma exacerbation, and greater improvements were observed after exacerbation with salmeterol compared with higher dose FP.. Salmeterol plus low-dose FP was more effective than higher dose FP alone in reducing asthma exacerbations in patients with persistent asthma. The ability to detect deteriorating asthma and the severity of exacerbation was similar between groups.

Topics: Acute Disease; Administration, Inhalation; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Life Tables; Male; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Treatment Outcome

Mometasone furoate (MF; Schering-Plough, Madison, NJ), is a glucocorticoid with high local potency and low potential systemic availability.. To compare the relative efficacy and safety of a new formulation of MF, coupled with a recently designed dry powder inhaler (DPI), in the treatment of patients with moderate persistent asthma. Fluticasone propionate administered by Diskhaler (FP Diskhaler, 250 microg twice a day; Glaxo Wellcome, Research Triangle Park, NC) was used as an active control.. A randomized, parallel group, double-blind (for MF-DPI dosage), evaluator-blind (for MF-DPI vs FP) trial.. Sixty centers in 20 countries.. Seven hundred thirty-three patients with moderate persistent asthma on inhaled corticosteroid treatment.. Discontinuation of previous inhaled corticosteroid and initiation of one of four study treatments: three doses of MF-DPI (100, 200, and 400 microg twice daily) and one of FP (250 microg twice daily >12 weeks).. FEV1 (primary efficacy variable) was evaluated as the mean change from baseline to endpoint (last evaluable visit). All dosage groups showed improvement at endpoint. Only 400 microg twice daily of MF-DPI (+0.19 L) was statistically different from 100 microg twice daily of MF-DPI (+0.07 L; P = 0.02). MF-DPI (200 microg twice daily) and FP Diskhaler groups showed similar improvement (+0.16 L). Greater improvement in most secondary variables (forced expiratory flow between 25% and 75% of vital capacity, and morning and evening peak expiratory flows) also resulted from treatment with 200 or 400 microg twice daily of MF-DPI or with FP Diskhaler, compared with 100 microg twice daily of MF-DPI. Overall, a total daily 800-microg dose of MF-DPI conferred no significant additional benefit >400 microg of MF-DPI. The incidence of oral candidiasis was 1%, 7%, 10%, and 10% in the 100, 200, and 400 microg twice daily of MF-DPI and FP groups, respectively.. A total daily dose of 400 microg of MF-DPI provides clinical benefit comparable to that observed with a total daily dose of 500 microg of FP Diskhaler.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Mometasone Furoate; Nebulizers and Vaporizers; Powders; Pregnadienediols; Pulmonary Ventilation; Sleep Initiation and Maintenance Disorders

Inhaled corticosteroids provide first-line treatment for asthma. An advance to improve potency was to produce new molecules with increased glucocorticoid receptor affinity (eg, fluticasone propionate [FP]). An alternative is to deliver more medication to both the large and small airway inflammation of asthma by using an extrafine aerosol (eg, beclomethasone dipropionate extrafine aerosol [BDP-extrafinel).. To demonstrate clinical equivalence of BDP-extrafine (400 microg daily) and FP (400 microg daily) in symptomatic asthmatic patients over the course of 6 weeks.. This was a double-blind, double-dummy, parallel-group, multicenter, 6-week study in adults with asthma taking conventional FP 100 to 250 microg daily or equivalent, and displaying signs/symptoms of active disease requiring additional therapy.. Eighty-eight patients were randomized to BDP-extrafine (and FP-placebo) and 84 to FP (and BDP-placebo). There were no significant differences between treatments with respect to symptom control, as evidenced by mean change from baseline in percentage days without asthma symptoms/nights without sleep disturbance observed at weeks 1 to 2, 3 to 4, or 5 to 6. Mean changes from baseline in AM PEFR at weeks 5 to 6 for BDP-extrafine (19.0) and FP (30.5) were equivalent (P = 0.022 for equivalence). There were significant (P < 0.001) within-treatment-group differences in mean change from baseline in AM PEFR at weeks 1 to 2 for both treatments. There was no difference in the incidence of patients reporting at least one adverse event during the study (BDP-extrafine 41%; FP 37%). Mean percentage change from baseline for AM plasma cortisol at week 6 was + 17.7% for BDP-extrafine and +4.2% for FP (P = 0.066 for difference).. BDP-extrafine and FP at doses of 400 microg daily provided equivalent asthma control in patients with symptomatic asthma and exhibited similar safety profiles.

Topics: Adolescent; Adult; Aerosols; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Particle Size; Peak Expiratory Flow Rate; Safety; Treatment Outcome

This study was carried out in an attempt to compare the efficacy and safety of fluticasone propionate (FP) at the half dose of budesonide (BUD) and beclamethasone dipropionate (BD) in childhood asthma. Ninety-six children with moderate to severe asthma (9.6 +/- 2.17 years) whose asthma was already controlled on BUD (n = 52) or BD (n = 44) were recruited into the study. In the first part of the study (the first 12 weeks) each group was followed with three weekly lung function measurements, daily diary records, and peak expiratory flow (PEF) measurements on the initial medication. At the end of 6 weeks, drugs were switched to a half dose of FP, and the subjects were followed for another 6 weeks. Blood samples were obtained for osteocalcin and plasma cortisol levels after each treatment period. In the second part of the study, 50 patients continued to take FP at the half dose of BUD or BD for another 30 weeks. Clinic visits, including lung function and PEF measurements, were conducted every 10 weeks. After 6 weeks of FP treatment, there was a small but statistically significant decrease in FEV1 and FEF(25-75) in both groups (BUD and BD) without any significant obstruction. These mild changes in lung function measurements continued during long-term follow-up. However, there was no statistically significant further decrease in any lung function parameters while receiving FP (visits 3-8) (coefficient = -0.00751 L/day, p = 0.39 for FEF(25-75) and coefficient = -0.00910 L/sec/day, p = 0.055 for FEV1). There were no significant changes in the morning and evening PEF measurements and diurnal PEF variations after 6 weeks of treatment with FP compared with BUD and BD treatments. There were no significant changes in basal cortisol and osteocalcin levels before or after 6 weeks of FP treatment (p > 0.05). The present study concluded that, although FP at the half dose of BUD or BD seems to maintain reasonable control of the disease symptoms, a mild but significant and persistent decrease in lung function parameters may indicate that FP may not be twice as potent as BUD or BD in childhood asthma by evaluation of lung functions. This conclusion must be further verified with long-term studies.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Child; Female; Fluticasone; Follow-Up Studies; Humans; Male; Respiratory Function Tests; Time Factors

The role of inhaled corticosteroids for the treatment of wheeze in infancy remains unclear.. To investigate the effect of inhaled fluticasone on symptoms in a group of wheezy infants who had a high risk of progressing to childhood asthma.. A total of 52 infants, under 1 year of age, with a history of wheeze or cough and a history (personal or first degree relative) of atopy were prescribed either 150 microg fluticasone twice daily (group F) or placebo (group P), via metered dose inhaler, for 12 weeks following a two week run in period. Symptoms were scored in a parent held diary and the mean daily symptom score (MDS) and symptom free days (SFD) calculated for each two week period.. Thirty seven infants completed the study. Both MDS and SFD improved significantly between the run in and final two week period in group F, but not group P, with a mean difference in change (95% CI) between groups of 1.12 (0.05 to 2.18) for MDS and median difference of 3.0 (0.002 to 8.0) for SFD.. Improvement of clinical symptoms in response to fluticasone can be shown in this high risk group of infants. In the absence of effective alternatives inhaled corticosteroids should be considered in this patient group.

Topics: Administration, Inhalation; Airway Resistance; Androstadienes; Asthma; Double-Blind Method; Female; Fluticasone; Functional Residual Capacity; Glucocorticoids; Humans; Immunoglobulin E; Infant; Linear Models; Male; Respiratory Sounds; Statistics, Nonparametric; Treatment Outcome

The objective of our study was to compare the efficacy and safety of fluticasone propionate (an inhaled corticosteroid) with zafirlukast (a leukotriene modifier) for persistent asthma.. In this randomized placebo-controlled, parallel-group, double-blind, double-dummy trial, patients underwent an 8- to 14-day run-in period followed by 12 weeks of treatment with inhaled fluticasone propionate (88 mg twice daily by metered-dose inhaler), oral zafirlukast (20 mg twice daily), or placebo.. We included a total of 338 persistent asthma patients, 12 years of age or older, using short-acting b2-agonists alone.. measured Efficacy outcomes included changes in pulmonary function, asthma symptoms, rescue albuterol use, nighttime awakenings due to asthma, and quality of life. Safety outcomes included asthma exacerbations, adverse events, and clinically significant laboratory test results.. After 12 weeks of treatment, patients taking fluticasone propionate experienced significantly greater improvements in all clinical parameters (symptom scores, percentages of symptom-free and albuterol-free days, albuterol use, and nighttime awakenings) compared with patients taking zafirlukast (P <.05) or placebo (P <.05). Treatment with fluticasone propionate resulted in significantly greater improvements in pulmonary function compared with zafirlukast (P <.05) or placebo (P <.05). Fewer fluticasone propionate patients (4%) had an exacerbation requiring oral corticosteroids compared with those taking zafirlukast (12%) or placebo (10%).. Inhaled fluticasone propionate is more effective than zafirlukast in controlling asthma symptoms, improving pulmonary function, and improving quality of life for patients who are symptomatic with the use of short-acting b2-agonists alone.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Double-Blind Method; Female; Fluticasone; Humans; Indoles; Leukotriene Antagonists; Male; Middle Aged; Patient Satisfaction; Phenylcarbamates; Respiratory Function Tests; Sulfonamides; Tosyl Compounds

The impact of switching from other inhaled corticosteroids to fluticasone propionate was studied in patients with severe oral-steroid-dependent asthma over a 1-year period. In this open-label prospective study, patients on maintenance doses of oral and inhaled steroids were referred to a national asthma treatment center and were switchedfrom their previous inhaled corticosteroid to fluticasone propionate 880 microg BID. Compared with data collected from the year prior to enrollment, treatment with fluticasone propionate resulted in significant improvements in pulmonary function, oral steroid requirements, and health resource utilization. In addition, five patients were completely weaned off oral steroids.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Colorado; Costs and Cost Analysis; Female; Fluticasone; Humans; Male; Middle Aged; Outpatient Clinics, Hospital; Prednisone; Prospective Studies; Referral and Consultation; Respiratory Function Tests; Treatment Outcome; United States

To compare the short-term efficacy and safety of low-dose fluticasone propionate with that of oral zafirlukast therapy for patients previously treated with beta-2-agonists alone, and to evaluate the potential therapeutic benefit of switching from zafirlukast to a low-dose inhaled corticosteroid.. This study consisted of a 4-week randomized, double-blind treatment period followed by a 4-week open-label period. Two hundred ninety-four patients > or =12 years old with asthma previously uncontrolled with beta-2-agonists alone were randomly assigned to treatment with low-dose inhaled fluticasone (88 microg twice daily) or oral zafirlukast (20 mg twice daily). After 4 weeks, all patients discontinued their double-blind therapy and received open-label fluticasone (88 microg twice daily). Outcomes included pulmonary function, asthma symptoms, albuterol use, asthma exacerbations, and adverse events.. During the double-blind treatment period, fluticasone patients had significantly greater improvements in morning peak flow (29.3 L/min vs. 18.3 L/min), percentage of symptom-free days (19.8% vs. 11.6%), and daily albuterol use (-1.8 puffs per day vs. -1.1 puffs per day) compared with zafirlukast patients (P < or =0.025, each comparison). During the open-label treatment period, patients switched from zafirlukast to fluticasone experienced additional improvements in morning peak flow (17.2 L/min), evening peak flow (13.6 L/min), and FEV(1) (0.11 liter) and daily albuterol use (-0.9 puffs daily) compared with values obtained at the end of the double-blind treatment period (P < or =0.001, each comparison).. Low-dose fluticasone was more effective than zafirlukast in improving pulmonary function and symptoms in patients with persistent asthma. In addition, switching patients from zafirlukast to fluticasone further improved clinical outcomes.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Indoles; Lung; Male; Middle Aged; Phenylcarbamates; Respiratory Function Tests; Sulfonamides; Time Factors; Tosyl Compounds; Treatment Outcome

We studied the effects of fluticasone propionate (FP) inhalation and the airway inflammation in beclomethasone dipropionate (BDP)-resistant bronchial asthma. Twenty-five patients who had used BDP and whose mean PEF was less then 80% were enrolled in this study. After 2 weeks of BDP inhalation. FP inhalation was administered. The total eosinophil count in the peripheral blood (/microliter), their percentage of the total WBC count (% Eos), the count in induced sputum, the serum ECP content and the induced sputum ECP content were measured before and after 6 weeks of FP treatment. There was a significant increase of morning and evening PEF, from 63.1% to 76.1% and from 63.6% to 76.2%, respectively. There was a significant positive correlation between the peripheral blood % Eos and the % increase of PEF (p < 0.01). There was also a significant positive correlation between the induced sputum % Eos and the % increase of PEF (p < 0.05). The induced sputum ECP content was still as high as 180 micrograms/l after FP treatment. The mean % PEF did not reach 80% after FP treatment. This study suggests that airway inflammation persists in some severe asthma patients despite inhalation of FP 800 micrograms.

Topics: Administration, Inhalation; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biomarkers; Blood Proteins; Drug Resistance; Eosinophil Granule Proteins; Female; Fluticasone; Humans; Inflammation Mediators; Male; Middle Aged; Peak Expiratory Flow Rate; Ribonucleases; Sputum; Treatment Outcome

The objective of this study was to determine whether initial maintenance therapy for the treatment of inflammation and bronchoconstriction associated with persistent asthma is more effective with a combination product (100 microg of fluticasone propionate and 50 microg of salmeterol [FSC]) administered twice daily through the Diskus device (GlaxoWellcome, Research Triangle Park, NC) or with montelukast at 10 mg once daily. A 12-wk, randomized, double-blind, double-dummy, multicenter study was conducted with 423 patients 15 yr of age and older with asthma and who were symptomatic while receiving short-acting beta(2)-agonists alone. At end point, FSC resulted in significantly greater increases in morning predose FEV(1) (0.54 +/- 0.03 vs. 0.27 +/- 0.03 L), morning peak expiratory flow (PEF) (89.9 +/- 6.7 vs. 34.2 +/- 4.7 L/min), evening PEF (69.9 +/- 5.8 vs. 31.1 +/- 4.5 L/min), the percentage of symptom-free days (48.9 +/- 2.9 vs. 21.7 +/- 2.5%), the percentage of rescue-free days (53.0 +/- 2.8 vs. 26.2 +/- 2.5%), and the percentage of nights with no awakenings (23.0 +/- 2.5 vs. 15.5+/-2.4%) compared with montelukast (p < or = 0.001, all comparisons). FSC significantly reduced asthma symptom scores (-1.0 +/- 0.1 vs. -0.6 +/- 0.1), rescue albuterol use (-3.3 +/- 0.2 vs. -1.9 +/- 0.2 puffs/d), and the number of exacerbations (0 vs. 11) compared with montelukast (p < 0.001). Both treatments were well tolerated. In summary, treatment of the two main components of asthma (inflammation and bronchoconstriction) with fluticasone propionate and salmeterol in a combination product was a more effective initial maintenance treatment strategy than treatment with montelukast, a single-mediator antagonist.

Topics: Acetates; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Quinolines; Salmeterol Xinafoate; Sulfides

High-dose inhaled corticosteroids (ICS) have been associated with the same side-effects as oral corticosteroids. Beclomethasone dipropionate (BDP) and budesonide (BUD) in doses greater than 2000 microg/day are used regularly in severe asthma, despite the fact that safety and efficacy data at such high doses are limited. Fluticasone propionate (FP) has been promoted as being twice as potent clinically as BDP or BUD at doses of 2000 microg/day or less with a similar safety profile. The aim of this study was to compare the efficacy and safety of FP with BDP and BUD in 133 symptomatic adult asthmatics requiring at least 1750 microg/day of BDP or BUD.. Patients fulfilling the entry criteria were randomized to receive either their regular ICS medication or FP at approximately half the microgram dose for 6 months in an open, parallel group study. The primary efficacy measure was based on morning peak expiratory flow measurements recorded by patients on daily record cards, while determination of safety was based on a number of endpoints including changes in bone turnover indices, the incidence of topical side-effects and assessments of quality of life.. It was shown that patients who were switched to FP, but not those continuing with BDP or BUD, had significant increases in levels of morning serum cortisol and the urine cortisol:creatinine ratio while maintaining asthma control. Serum osteocalcin and the pyridinoline:creatinine ratio, as well as the deoxypyridinoline:creatinine ratio, were also shown to increase only in the FP group. Subjective assessments such as quality of life score, the incidence and ease of bruising, and reports of hoarseness also favoured the FP group.. It is concluded that, at the doses studied and with the delivery devices used clinically, FP is at least as effective as BDP/BUD in the management of severe asthma and may offer clinical advantages with respect to steroid-related adverse effects.

Topics: Adult; Androstadienes; Asthma; Beclomethasone; Biomarkers; Budesonide; Chronic Disease; Contusions; Creatinine; Female; Fluticasone; Glucocorticoids; Hoarseness; Humans; Hydrocortisone; Male; Middle Aged; Osteocalcin; Quality of Life

Inhaled steroids play a very important role in the prevention and treatment of asthma. Previous studies indicated that fluticasone propionate (FP) had low bioavailability and high local potency. However, the laboratory data in these studies were not obtained among Taiwan population. It is very important that native data should be established. Thus a 12-week research program was designed, involving 77 patients, 51 for FP group and 26 for beclomethasone dipropionate (BD) group. The objects were victims of moderate to severe asthma and their age ranged from 4 to 14 years old. An open, comparative and randomized method was adopted. Except for the 4-week-later daytime symptom score(P = 0.033, BD group was better), no other significant differences were found between the two groups in the symptom score improvement(P > 0.05). All the P-values for the daytime & night-time scores were lower than 0.001, which means obvious improvement after treatment in both groups. P-value for PEF improvement was 0.003 after 4 weeks (BD group was better) and 0.943 after 8 weeks; for FEV1 improvement, it was 0.005 after 4 weeks(BD group was better) and 0.252 after 8 weeks; and for FEV1/FVC improvements, it was 0.067 after 4 weeks and 0.097 after 8 weeks. There was no statistic significance in total eosinophil count (TEC), IgE, eosinophil cationic protein (ECP) serum level changes after 4 or 8 weeks. Adverse effects were all anticipated and no statistic significance showed up, either, between the two groups or in the cortisol levels (P > 0.05). In conclusion, native data indicated that the potency of 100 micrograms of FP was equal to that of 200 micrograms of BD and that few side effects were noted in FP group. It is recommended that this drug be introduced for clinical use.

Topics: Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Blood Proteins; Child; Child, Preschool; Eosinophil Granule Proteins; Eosinophils; Female; Fluticasone; Humans; Immunoglobulin E; Male; Ribonucleases

Many uncertainties remain in the diagnosis and treatment of preschool children with asthma symptoms.. We sought to determine the subgroups of preschool children (aged 12-47 months) with recurrent asthma symptoms most likely to respond to inhaled fluticasone propionate (200 microg/d).. Subgroups of pooled data from 2 similar 12-week multicenter studies were analyzed.. Children with frequent symptoms (symptoms on > or =3 days per week and a total of > or =75% days with symptoms during the 4-week run-in period; n = 169) showed a significantly greater increase in days without symptoms after fluticasone propionate treatment (0% to 45%) compared with after placebo treatment (0% to 25%, P =.005). Children with a family history of asthma (n = 213) also had a significantly greater increase in days without symptoms after fluticasone propionate (11% to 54%) compared with after placebo (7% to 35%, P =.002) and a significantly higher proportion of exacerbation-free patients (61% to 76%, P =.02). Children with less frequent symptoms, no family history of asthma, or both showed no significant treatment effect. There seemed to be no association between response to fluticasone propionate and history of rhinitis or eczema or the number of previous exacerbations.. Children with frequent symptoms, a family history of asthma, or both showed the greatest response to fluticasone propionate treatment. These findings may help to predict treatment outcome and guide the management of preschool children with recurrent asthma symptoms.

Topics: Administration, Inhalation; Age Factors; Androstadienes; Anti-Asthmatic Agents; Asthma; Child, Preschool; Double-Blind Method; Eczema; Family Characteristics; Female; Fluticasone; Humans; Infant; Male; Nebulizers and Vaporizers; Placebos; Respiratory Sounds; Rhinitis

To compare the relative value of an inhaled corticosteroid, fluticasone propionate 88 microg twice daily, versus an oral leukotriene receptor antagonist, zafirlukast 20 mg twice daily, in patients with persistent asthma currently receiving short acting beta2-agonists alone.. A cost-efficacy analysis using resource utilisation and clinical data obtained prospectively from a multicentre, randomised, double-blind, double-dummy, placebo-controlled 12-week clinical trial conducted in the US.. Third-party payor.. A total of 451 corticosteroid-naive patients with persistent asthma were treated with either fluticasone propionate 88 microg twice daily or zafirlukast 20 mg twice daily. All patients were given salbutamol (albuterol) to be used as rescue medication. Data were examined using intent-to-treat analysis.. Mean daily per person cost-efficacy ratios using improvement in forced expiratory volume in 1 second (FEV1) [> or = 12% increase from baseline] were $US 3.47 for fluticasone propionate compared with $US 7.81 for zafirlukast (1999 values). The mean daily per person cost-efficacy ratios for symptom-free days obtained were $US 5.51 for fluticasone propionate compared with $US 14.98 for zafirlukast. These cost-efficacy ratios remained in favour of fluticasone propionate after a robust sensitivity analysis.. Treatment with fluticasone propionate 88 kg twice daily was the most cost effective treatment compared with zafirlukast 20 mg twice daily in this 12-week clinical trial. This analysis supports the use of fluticasone propionate 88 microg twice daily as first-line treatment in patients with persistent asthma previously treated with short-acting beta2-agonist alone.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Cost-Benefit Analysis; Female; Fluticasone; Hospitalization; Humans; Indoles; Male; Phenylcarbamates; Randomized Controlled Trials as Topic; Sulfonamides; Tosyl Compounds; Treatment Outcome

ACTH regulates adrenal androgen production, which may thus be reduced during glucocorticosteroid therapy. Dehydroepiandrosterone sulfate is the most abundant androgen secreted by the adrenals. We wished to evaluate whether serum levels of dehydroepiandrosterone sulfate can be used as an indicator of adrenal suppression during inhaled steroid treatment in children. Sixty school-aged children with newly diagnosed asthma were randomly divided into budesonide (n = 30) and fluticasone propionate (n = 30) groups. Fifteen cromone-treated children served as a control group. The budesonide dose was 800 microg/d during the first 2 months and 400 microg/d thereafter. The respective fluticasone propionate doses were 500 and 200 microg/d. Serum dehydroepiandrosterone sulfate concentrations were measured before and after 2 and 4 months of treatment. In the budesonide group, serum dehydroepiandrosterone sulfate decreased from the baseline by a mean of 21% (95% confidence interval, 13-29%; P < 0.001) after 2 months of high dose treatment and by 16% (95% confidence interval, 8-25%; P < 0.001) after 4 months of treatment. In the fluticasone propionate group, the respective figures were 10% (95% confidence interval, 4-16%; P < 0.01) and 6% (95% confidence interval, 16% decrease-3% increase; P = NS). A low dose ACTH test indicated adrenocortical suppression at 4 months in 14 (23%) steroid-treated children. In these children, dehydroepiandrosterone sulfate decreased by a mean of 21% (95% confidence interval, 14-28%), whereas in those 46 steroid-treated children with normal ACTH test results, dehydroepiandrosterone sulfate decreased by 8% (95% confidence interval, 0-16%; P < 0.05 between these groups). In the control group, dehydroepiandrosterone sulfate levels tended to increase (by a mean of 26%), reflecting the normal physiological change at this age. In conclusion, inhaled steroid treatment suppresses dehydroepiandrosterone sulfate production in a dose-dependent manner. Monitoring of serum dehydroepiandrosterone sulfate concentrations can be used as a practical method to follow adrenocortical function and to detect its suppression during inhaled steroid treatment in children.

Topics: Administration, Inhalation; Adrenocorticotropic Hormone; Androstadienes; Asthma; Budesonide; Child; Dehydroepiandrosterone Sulfate; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; Male

It has been suggested in cross-sectional studies that provocation with adenosine 5'-monophosphate (AMP) more closely reflects the inflammatory process in asthma than does provocation with methacholine or histamine. We investigated whether the steroid-induced improvement in the provocative concentration of AMP producing a 20% decline in FEV1 (PC20 AMP) is more closely associated with the concomitant reduction in airway inflammation than is the improvement in PC20 methacholine. In 120 asthmatic patients, we measured PC20 methacholine and PC20 AMP as well as sputum induction and nitric oxide (NO) in exhaled air before and after 2 weeks of treatment with corticosteroids. Improvement in PC20 AMP was solely related to reduction in airway inflammation (i.e., change in the number of sputum eosinophils, lymphocytes, epithelial cells, and concentration of NO in exhaled air). In contrast, improvement in PC20 methacholine was related to both reduction in airway inflammation (i.e., change in the number of sputum eosinophils and lymphocytes) and increase in FEV1 %predicted. The total explained variance of the improvement in bronchial hyperresponsiveness was greater for AMP than for methacholine (36% versus 22%, respectively). We conclude that PC20 AMP is more sensitive to changes in acute airway inflammation than is PC20 methacholine, further reinforcing the notion that PC20 AMP can be a useful tool for monitoring the effects of antiinflammatory therapy.

Topics: Adenosine Monophosphate; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Inflammation; Male; Methacholine Chloride; Multivariate Analysis; Prednisone

Exhaled nitric oxide (ENO) is a noninvasive marker of ongoing inflammation in asthmatic patients. Comparison between inhaled and oral anti-inflammatory medications in reduction of ENO in asthmatic patients has not been performed.. We measured changes in ENO, spirometry, need for rescue medication, quality of life (QOL), and diary scores (DS) after inhaled and oral anti-inflammatory therapy in adults with moderate asthma.. A randomized, double-blind, placebo-controlled, crossover design with 4-week washout periods was used. A plateau level of ENO, measured in parts per billion (ppb), was obtained by chemiluminescence with a Sievers 280NOA as per American Thoracic Society recommendations. Eighteen asthmatic adults (15 Hispanic, with a percentage predicted forced expiratory volume in 1 second (FEV1%) of 50% to 85%) on bronchodilators (beta2) only were studied. Subjects used fluticasone propionate (FP) metered-does inhaler (44 microg), two puffs twice daily, and matching placebo (PB) for 4 weeks. Eight of the asthmatic patients (7 Hispanic, FEV1% 50% to 85%) on bronchodilators only then received blinded zafirlukast (ZK) 20 mg and matching PB twice daily for 4 weeks.. Low-dose inhaled FP resulted in significant improvements in ENO, spirometry, QOL, DS, and beta2 use. A significant difference in mean ENO was found (P < 0.01) before and after FP from 34+/-7 ppb to 13+/-3 ppb. A significant improvement was found (P < 0.05) with FEV1% from 75+/-3 to 85+/-3 with FP treatment. The other measured parameters, percentage predicted of peak expiratory flow rate, beta2 need, DS, and QOL measurements, were improved with low-dose FP treatment. No significant reduction was found in ENO with oral ZK for 4 weeks. After oral ZK washout and the second extension arm of placebo, ENO significantly increased back to 47+/-14 ppb (P < 0.05), but spirometry measures did not worsen. Significant improvements were found with DS and beta2 use with oral ZK therapy.. These results reveal ENO is reduced with only low-dose inhaled FP in asthmatic patients not on anti-inflammatory medication. In the smaller extension study, ENO was reduced with FP and not with oral ZK treatment, and ENO levels increased back to near prestudy levels after ZK washout and the second extension arm of placebo. As a marker of inflammation, ENO levels reveal an improvement with anti-inflammatory medication and worsening when it is discontinued.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Biomarkers; Breath Tests; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Indoles; Leukotriene Antagonists; Male; Middle Aged; Nitric Oxide; Phenylcarbamates; Sulfonamides; Tosyl Compounds

To compare the long-term effect of treatment with fluticasone propionate or beclomethasone dipropionate on growth in asthmatic children.. Prospective, multicenter, randomized, double-blind, parallel-group study.. Children requiring regular treatment with inhaled corticosteroids and with a sexual maturity rating of Tanner stage 1 (prepubertal).. Three hundred forty-three children aged 4 to 11 years with asthma. The growth population (excluding patients with protocol violations likely to affect growth measurements) included 277 patients.. Fluticasone propionate or beclomethasone dipropionate, both at a dosage of 200 microg administered twice daily via a dry powder inhaler (Diskhaler) for 12 months.. Growth velocity, lung function, and serum and urinary cortisol levels.. The adjusted mean growth velocity in the fluticasone group was significantly greater than that in the beclomethasone group (5.01 [SE, 0.14] vs 4.10 [SE, 0.15] cm/y; difference, 0.91 cm; 95% confidence interval, 0.63-1.20 cm; P<.001). Both treatments improved lung function, with significant differences in favor of fluticasone. Adverse events were similar in both groups, and there were no significant differences in effect on serum and urinary cortisol levels.. The more favorable risk-benefit ratio of fluticasone indicates that this agent is preferable to beclomethasone for the long-term treatment of children with asthma, especially if moderate doses are required.

Topics: Androstadienes; Asthma; Beclomethasone; Body Height; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Hydrocortisone; Male; Prospective Studies

Suppression of the hypothalamic-pituitary-adrenal (HPA) axis, a potential systemic effect of inhaled corticosteroid therapy, can be quantified by monitoring serum, urinary, and salivary cortisol levels.. 1) Compare the effects on HPA axis of the inhaled corticosteroids flunisolide and fluticasone propionate versus placebo and oral prednisone. 2) Estimate dose-potency ratio for HPA-axis suppression.. Multicenter, randomized, placebo-controlled, open-label, 21-day trial. Active regimens were flunisolide 500 and 1,000 microg, twice daily; fluticasone propionate 110, 220, 330, and 440 microg, twice daily; and prednisone, 7.5 mg daily. Enrolled patients were nonsmokers, 18 to 50 years of age, with persistent mild-to-moderate asthma and had not used oral, nasal, or inhaled corticosteroids for 6 months before study. Main outcome measures were area under serum cortisol concentration curve for 22 hours (AUC(0-22h)); 24-hour urinary cortisol level; and 8 AM salivary cortisol level.. One hundred fifty-three patients were randomly assigned to active treatment or placebo; 125 patients completed the study and were at least 80% compliant with their regimens. Both fluticasone propionate and flunisolide caused dose-dependent suppression of HPA axis, which was statistically greater for fluticasone propionate (P = 0.0003). Dose-potency ratio showed 4.4 times more serum-cortisol suppression/microgram increase in dose with fluticasone propionate than with flunisolide. Diurnal pattern of serum cortisol suppression was persistent with fluticasone propionate and "remitting" with flunisolide. Salivary and urinary cortisol data were qualitatively similar to serum cortisol results.. Fluticasone caused significantly more suppression of HPA axis than flunisolide. Flunisolide may provide a safe option for patients with asthma requiring long-term inhaled corticosteroid therapy.

Topics: Administration, Inhalation; Adrenal Glands; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Area Under Curve; Asthma; Dose-Response Relationship, Drug; Female; Fluocinolone Acetonide; Fluticasone; Humans; Hydrocortisone; Hypothalamus; Kinetics; Male; Pituitary Gland

To determine the basal pharmacokinetics, lung uptake and plasma cortisol suppression for two commonly prescribed inhaled corticosteroids.. Twenty-one subjects (13 healthy and 8 mild asthmatic patients) received fluticasone propionate via a chlorofluorocarbon-propelled pressurized metered-dose inhaler (pMDI) (healthy subjects only) and Diskus and budesonide via Turbuhaler, 1000 microg twice daily for 7 days. Intravenous doses (200 microg) of both compounds were used as references. Plasma concentrations of fluticasone and budesonide were determined during 48 h by liquid chromatography plus tandem mass spectrometry (LC-MS-MS). Plasma concentrations of cortisol were determined by LC-MS every second hour for 24 h at baseline, and following each treatment.. The volume of distribution was found to be larger and the elimination half-life and mean absorption time longer for fluticasone than for budesonide. The systemic availability of budesonide via Turbuhaler (39%) was significantly higher than that of fluticasone via Diskus (13%) (ratio 3.0 [2.5, 3.6] with 95% confidence interval [CI]), and via pMDI (21%) (ratio 1.8 [1.3, 2.3]). In addition, at steady state the systemic availability of fluticasone via pMDI was significantly higher than via Diskus (ratio 1.6 [1.1, 2.2]). The lung deposition of budesonide via Turbuhaler was 2.2-fold [1.7, 2.9] higher than that of fluticasone pMDI and 3.4-fold [2.8, 4.0] higher than that of fluticasone Diskus. In addition, the lung deposition of fluticasone via pMDI was 1.5-fold [1.1, 2.9] higher than that via the Diskus inhaler. Plasma cortisol (24 h) was significantly reduced vs baseline for all three treatments. The cortisol concentration vs baseline was 12% for fluticasone pMDI, which was significantly lower (ratio 0.32 [0.24, 0.42]) than that for fluticasone Diskus (39%), and for budesonide Turbuhaler (46%) (ratio 0.27 [0.21, 0.37]). The plasma cortisol concentration did not differ significantly between treatments with fluticasone Diskus and budesonide Turbuhaler (ratio 0.87 [0.65; 1.15]).. Budesonide and fluticasone differ in their pharmacokinetic properties in that although clearance is the same, the rate of uptake and elimination is slower for fluticasone. Despite a significantly higher pulmonary availability of budesonide via Turbuhaler, the plasma cortisol suppression is less than that of fluticasone via pMDI and similar to that of fluticasone via Diskus. There is no indication of any difference between healthy subjects and mild asthmatic patients in the pharmacokinetics and plasma cortisol suppression of fluticasone and budesonide.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Area Under Curve; Asthma; Budesonide; Cross-Over Studies; Female; Fluticasone; Humans; Hydrocortisone; Injections, Intravenous; Lung; Male; Middle Aged; Models, Biological; Peak Expiratory Flow Rate

Dose-dependent effects of inhaled corticosteroids have been described. Although it has been advised to start treatment with inhaled corticosteroids with a high dose tapering off subsequently (stepdown approach), no clinical studies have assessed this strategy. We compared two different dosage schedules of inhaled fluticasone propionate (FP) in chronic persistent childhood asthma with respect to efficacy (airways hyperresponsiveness [PD(20)], lung function, exhaled nitric oxide [eNO]) and safety (height). During this double-blind study, children with asthma (aged 6-10 yr) were randomized to receive either FP 200 microg/d (constant dose approach) or to start with 1000 microg/d with two monthly reductions to 500, 200, and 100 microg/d (stepdown approach). PD(20) improved in both approaches during treatment with FP, with a significantly better PD(20) after 2 mo of 1000 microg/d followed by 500 microg/d in the stepdown approach versus 200 microg/d in the constant dose approach. No significant differences in PD(20) or other efficacy parameters were found after 1 yr. Changes in standing height were similar in both treatment approaches. This study showed no superior clinical effect of a stepdown approach compared with a constant dose strategy of FP for 1 yr in children with chronic persistent asthma.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Body Height; Breath Tests; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Child; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluticasone; Forced Expiratory Volume; Humans; Methacholine Chloride; Nitric Oxide; Time Factors

To evaluate the cost-effectiveness of inhaled fluticasone propionate (FP) in children aged 12 to 47 months with asthma symptoms.. A retrospective economic analysis conducted from the perspective of the Danish health-care system, based on clinical data from a 12-week study.. Thirty-three outpatient centers in nine countries.. Two hundred thirty-seven children aged 12 to 47 months with documented history of recurrent wheeze or asthma symptoms.. Two dosages of FP, 100 microg/d and 200 microg/d, and placebo administered in two divided doses via a metered-dose inhaler and a Babyhaler (Glaxo Wellcome; Middlesex, UK) spacer device.. Effectiveness in terms of asthma exacerbations, control of cough and wheeze symptoms, symptom-free days, overall direct costs of asthma management in Danish kroner at 1999 prices, and mean and incremental cost-effectiveness ratios.. FP, 200 microg/d, was significantly more effective than placebo treatment in terms of the proportion of exacerbation-free patients (73.7% vs 59.8%; p = 0.025) and patients experiencing a > or = 25% improvement in cough symptoms (57.9% vs 39.0%; p = 0.018). The costs per exacerbation-free patient, per patient with a > or = 25% improvement in cough and wheeze symptoms from baseline, and per symptom-free day were lower in the FP groups than in the placebo group. The incremental cost-effectiveness ratios for these end points indicated that the additional benefits of FP, 200 microg/d, were achieved at a lower overall cost compared with placebo treatment.. From the perspective of the Danish health-care system, FP, 100 microg bid, administered via the Babyhaler inhalation device was cost-effective relative to standard therapy with bronchodilators alone.

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Child, Preschool; Cost-Benefit Analysis; Denmark; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Infant; Male; National Health Programs; Nebulizers and Vaporizers; Retrospective Studies; Treatment Outcome

We determined whether inhaled corticosteroid therapy modulates the expression of the transcription factor, nuclear factor kappa B (NF-kappaB), in patients with asthma. Fifteen stable patients with mild asthma underwent bronchoalveolar lavage (BAL) with bronchial biopsies in a double-blind, placebo-controlled and crossover study after placebo or after inhaled fluticasone propionate (500 microg twice daily). Fluticasone reduced the number of eosinophils in BAL fluid (BALF) and in airway biopsies, together with an improvement of bronchial responsiveness to methacholine. However, NF-kappaB DNA-binding in alveolar macrophages and in bronchial biopsies was not affected by fluticasone treatment. NF-kappaB expression was also measured by immunohistochemical staining with an antibody to the p65 component of NF-kappaB. Fluticasone caused an increase in the number of positive nuclear staining cells in the airway epithelium from 34. 1 +/- 5.0 to 64.1 +/- 8.0 per mm(2) (p = 0.002). In vitro studies of A549 epithelial cells stimulated by interleukin-1beta (IL-1beta) showed that dexamethasone increased p65 protein expression analyzed by Western blot. Despite an anti-inflammatory effect of fluticasone, there was no decrease in NF-kappaB-DNA binding and activation, indicating that this may not be a mechanism by which corticosteroids act in asthma. The significance of corticosteroid-induced increase in p65 protein expression is not known.

Topics: Administration, Inhalation; Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Blotting, Western; Bronchi; Bronchoalveolar Lavage Fluid; Calcium-Binding Proteins; Cell Count; Cells, Cultured; Cross-Over Studies; Dexamethasone; DNA; Double-Blind Method; Eosinophils; Epithelial Cells; Female; Fluticasone; Glucocorticoids; Humans; Interleukin-1; Macrophages, Alveolar; Male; Membrane Glycoproteins; Nerve Tissue Proteins; NF-kappa B; Receptors, Cell Surface; Synaptotagmin I; Synaptotagmins

Topics: Administration, Inhalation; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bias; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Fluticasone; Humans; Research Design; Salmeterol Xinafoate; Triamcinolone Acetonide

Three hundred forty-nine patients with asthma previously treated with medium doses of inhaled corticosteroids during a 2-wk, single-blind, run-in period were randomized to treatment with salmeterol 50 microg combined with fluticasone propionate (FP) 250 microg, salmeterol 50 microg, FP 250 microg, or placebo, each given twice daily through a Diskus device for 12 wk. Mean change in FEV(1) at endpoint was significantly (p

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Equipment Design; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Powders; Salmeterol Xinafoate; Single-Blind Method

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Glucocorticoids; Humans; Male

The dose dependency of the effects of inhaled corticosteroids on markers of asthmatic airway inflammation have not been well studied. There is a need to study the dose/response effects on this inflammation. In order to determine the dose/response effects of fluticasone propionate (FP), 24 asthmatic subjects were randomized to low- (100 microg x day(-1)) or high-dose (1,000 microg x day(-1)) FP for six weeks followed by placebo for 3 weeks. During treatment, the median increase in forced expiratory volume in one second (FEV1)was 12% in the high-dose group (p<0.05) and 10% in the low-dose group (p<0.05) (p>0.05 between groups); the median decrease in the percentage of sputum eosinophils was 93% in the high-dose group (p<0.05) and 46% in the low-dose group (p<0.05) (p>0.05 between groups). Symptoms, salbutamol use, morning peak flow, provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophil cationic protein concentration and tryptase activity improved significantly in both groups (p<0.05), but only the improvement in salbutamol use was greater in the high-dose group (p<0.05). During the run-out, the improvements in FEV1 and PC20 were rapidly reversed in both groups, but the improvements in peak flow and tryptase activity persisted; the improvement in sputum eosinophil concentration persisted only in the high-dose group (p<0.05). It was concluded that dose/response effects for FP are not easily demonstrable because low-dose FP is quite effective. For most outcomes, the effects of high- and low-dose FP are relatively short-lived after treatment is stopped. This finding raises questions about the extent to which inhaled corticosteroids are disease-modifying in asthma.

Topics: Administration, Inhalation; Administration, Topical; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged

A randomized double-blind placebo-controlled parallel group study with inhaled fluticasone propionate over 6 weeks, designed to quantify the beneficial effect on airway responsiveness, and so assess whether short pulses of intermittent prophylactic treatment might serve as an alternative means of managing mild asthma, is reported. The 20-50-yr-old participants, who were recruited from an epidemiological study of the general population, had never knowingly received any regular treatment for asthma. Fluticasone propionate at the maximum recommended dose level (2,000 microg daily) and placebo were administered via metered-dose inhalers, and airway responsiveness was quantified conventionally by the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PD20) at 2-week intervals during the treatment phase and at various intervals subsequently. Compared with placebo fluticasone propionate was associated with a highly significant decrease in airway responsiveness (1.9 doublings of the geometric mean PD20), which was maximal at the end of the 6-week treatment period. No persisting benefit was detectable at the next measurement 2 weeks later, or thereafter. Multiple linear regression analysis showed that the magnitude of the fluticasone propionate effect was significantly greater in males than in females (3.2 versus 1.2 doublings respectively of the geometric mean PD20), but was uninfluenced by current smoking, age or FEV1. In conclusion, in the absence of any possibility of tachyphylaxis, inhaled fluticasone propionate at this dose causes a steadily increasing improvement in airway responsiveness over a 6-week period, which is modified by sex but lost almost immediately on treatment cessation. Short pulses of intermittent prophylactic treatment would not, therefore, be useful as a means of managing mild asthma.

Topics: Administration, Inhalation; Administration, Topical; Adult; Airway Resistance; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchial Provocation Tests; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Sex Factors; Treatment Outcome

The aim of the present study was to evaluate the prevalence of adrenal suppression and growth retardation in children using moderate doses of budesonide or fluticasone propionate. Seventy-five asthmatic children were randomly divided into three treatment groups: 30 to the fluticasone propionate (FP), 30 to the budesonide (BUD), and 15 to the cromone (CROM) group. FP doses were 500 microg/day during the first 2 months and 200 microg/day thereafter. The respective BUD doses were 800 and 400 microg/day. A low dose ACTH (0.5 microg/1.73 m2) test was performed before treatment and 2, 4, and 6 months later. The test was considered abnormal if the stimulated serum cortisol concentration was more than 2 SD lower than the pretreatment mean (<330 nmol/L). The low dose ACTH test was abnormal after both the high and low steroid doses in 23% of the children. At the 4 month measurement there were more abnormal tests in the BUD (n = 9) than in the FP (n = 5) group (P < 0.05). At that time also the stimulated concentration of serum cortisol was lower in the BUD than in the CROM group (P < 0.01), whereas the difference between the FP and CROM groups was not significant. During the study year the mean decrease in height SD score was 0.23 in the children treated with BUD, 0.03 in the children treated with FP, and 0.09 in the children treated with CROM; the difference between the BUD and FP groups was significant (P < 0.05). In conclusion, the low dose ACTH test revealed mild adrenal suppression in a quarter of the children using moderate doses of inhaled steroids. A FP dose of 200 microg/day caused less adrenal and growth suppression than did a BUD dose of 400 microg/day.

Topics: Administration, Inhalation; Adolescent; Adrenal Glands; Adrenocorticotropic Hormone; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Cromolyn Sodium; Dose-Response Relationship, Drug; Female; Fluticasone; Growth; Humans; Hydrocortisone; Male; Nedocromil

Topically applied glucocorticosteroids (GS) have been shown to cause local vasoconstriction in normal skin and this phenomenon is commonly used to assess the potency of topical GS (McKenzie skin blanching test). The purpose of the present study was to determine if an inhaled GS, fluticasone propionate (FP), similarly leads to vasoconstriction in the airway mucosa and if subjects with and without asthma have differential vascular responsiveness to GS. In 10 nonsmokers with stable asthma and 10 nonasthmatic nonsmokers, airway mucosal blood flow (Qaw) expressed per milliliter of anatomical dead space and the forced expiratory volume in 1 s (FEV (1)) were determined before and serially after inhalation of FP (88 to 1,760 microg) or placebo. Baseline mean (+/- SE) Qaw was 55.1 +/- 1.0 and 44.2 +/- 1.1 microl x min(-1) x ml(-1) in subjects with and without asthma, respectively (p < 0.001). The corresponding mean FEV(1) values were 2.34 +/- 0.13 and 3.22 +/- 0.12 L (p < 0.001). FP at 880 microg but not placebo produced a transient decrease in mean Qaw with a nadir at 30 min and return toward baseline at 90 min post-inhalation; the maximum mean decrease was 37% in subjects with asthma and 21% in unaffected subjects (p < 0.01); 880 microg of FP was the lowest effective dose. FEV(1) did not change after FP administration in either group. These results demonstrate a transient vasoconstrictive action of inhaled FP in the airway mucosa, with a greater vascular responsiveness in subjects with asthma than in unaffected subjects. The measurement of Qaw may provide a more relevant means of assessing the potency of inhaled GS than the McKenzie skin blanching test. In addition, our observation suggests that inhaled GS have potentially beneficial effects in asthma that is not related to their antiinflammatory action.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Blood Flow Velocity; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Regional Blood Flow; Respiratory Mucosa; Vasoconstriction

This study was designed to compare the effects of low-dose inhaled fluticasone propionate (100 mcg twice daily) with those of the leukotriene antagonist, zafirlukast (20 mg twice daily), on bronchial hyper-responsiveness. The study recruited 30 patients (nine men, 21 women; mean age 45 years) with forced expiratory volume in 1 sec (FEV1) > 50% and airway reversibility to salbutamol > or =15%. This was a single centre, double-blind, double-dummy cross-over study, composed of two successive 2-week treatment periods, each preceded by a 2-4 week single-blind placebo period. Following 2 weeks of treatment with fluticasone propionate and zafirlukast, the mean provocational concentration causing a 20% fall in FEV1 (PC20) histamine was 1.61 mg ml(-1) (SD 2.34) and 0.99 mg ml(-1) (SD 1.74) respectively. Taking baseline differences into account, the difference between treatments was equivalent to 0.77 doubling doses of histamine (95% CI, 0.05-1.50; P=0.037). Morning peak flow values were significantly higher (17 l min(-1); P=0.049) after treatment with fluticasone propionate during the second week of treatment. Both treatments were well tolerated. The results of this short-term study show that compared with zafirlukast, a low dose of fluticasone propionate offers greater clinical benefit and is more cost effective.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Volume; Humans; Indoles; Leukotriene Antagonists; Male; Middle Aged; Peak Expiratory Flow Rate; Phenylcarbamates; Sulfonamides; Tosyl Compounds

This study was designed in order to establish the perception of breathlessness during rest and while breathing against resistance, in patients with asthma, before and after 8 weeks of inhaled glucocorticoids (IGC) treatment and to compare these parameters in patients with and without improvement in FEV1. Sixty-seven asthmatic patients, with moderate asthma, attending the asthma clinic, and 20 normal subjects were studied. After a 2-week run-in period, in which the subjects were asked to use exclusively beta2-agonists as needed, the asthmatic patients were randomized to receive either treatment with IGC, 250 microg of fluticasone propionate (FP) twice a day, via a diskhaler (47 patients), or to receive placebo (20 patients) and to serve as a control group, for 8 weeks. Spirometry and measurements for the sensation of dyspnoea were performed before and at the end of the treatment period. The mean dyspnoea score during breathing against resistance was significantly lower (P<0.05) in the patients with asthma than in normal subjects, before entering the study. Following 8 weeks of inhaled FP, there was a significant improvement in the mean dyspnoea score during breathing against resistance in the asthmatics receiving IGCs but not in the control group (P<005). In the study group 32 patients had an improved FEV1 > 15% and 15 patients did not. There was a statistically significant difference in perception of dyspnoea (P<0.01), between the group of patients with a improved FEV1 and the group of patients that were under IGC treatment without improvement in their FEV1. There was also a difference in the mean beta2-agonists consumption between the two groups (P<0.01). Asthmatic patients have a significantly lower perception of dyspnoea compared to normal subjects. IGC treatment was associated with increased perception of dyspnoea. However, this improvement was noted only in patients with improved FEV1, while the patients without improvement remained with an equal degree of dyspnoea perception and beta2-agonists consumption.

Topics: Administration, Inhalation; Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Dyspnea; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Perception; Time Factors; Vital Capacity

There is some concern that prolonged treatment with high doses of inhaled corticosteroids may have a detrimental effect on bone mass. The aim of this one year study was to investigate the effects of low and high doses of fluticasone propionate (FP) (400 microg/day and 750 microg/day) and beclomethasone dipropionate (BDP) (800 microg/day and 1500 microg/day) on bone mass and metabolism.. This was a multicentre, double blind, parallel group study involving 69 mild to moderate asthmatic subjects who were randomised to treatment as follows: 22 to FP400, 21 to BDP800, 13 to FP750, and 13 to BDP1500. Their mean age was 39 years, 67% were men, and all the women were premenopausal.. The results of peripheral quantitative computed tomographic (pQCT) measurements (primary variable) showed that, compared with baseline values, there was no loss of trabecular or integral (cortical and trabecular) bone in the distal radius or tibia in any of the patients over the 12 month study period. No consistent pattern emerged from the analysis of changes from baseline in markers of bone formation and resorption after six and 12 months of treatment.. The results of this study provide reassuring prospective one year data showing that inhaled corticosteroids, in the range of doses used, had no adverse effects on bone mass and metabolism in this group of asthmatic patients.

Topics: Administration, Inhalation; Administration, Topical; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biomarkers; Bone and Bones; Bone Density; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Prospective Studies

According to a recent hypothesis, airway smooth muscle regulates airway calibre mostly at high lung volume, whereas the mucosa and adventitia dimensions dominate at low lung volumes. It was thought that if inhaled steroids decrease the thickness of airway wall in asthma, then forced vital capacity (FVC), which reflects the functional changes at low lung volume, should decrease less during induced bronchoconstriction than flow at high volume. The study was conducted in 31 mild asthmatics under control conditions and during a methacholine challenge before and after 4-weeks treatment with inhaled fluticasone dipropionate (1.5 mg daily, 16 patients) or placebo (15 patients). After fluticasone dipropionate treatment, control forced expiratory volume in one second (FEV1), and maximal flow at 50% of control FVC during forced expiration after a maximal (V'max,50) and a partial inspiration (V'p,50) significantly increased. During methacholine challenge, FVC decreased less than did FEV1 or V'max,50, and so did inspiratory vital capacity compared to V'p,50. Both the provocative dose of methacholine causing a 20% fall in FEV1 and the bronchodilator effect of deep inhalation significantly increased. The latter was assessed by means of the regression coefficient of all V'max,50 plotted against V'p,50. No significant changes in these parameters occurred after placebo. These data show that inhaled steroids remarkably blunt the occurrence of gas trapping during induced bronchoconstriction in mild bronchial asthma, possibly due to their effect on airway wall remodelling.

Topics: Administration, Inhalation; Adult; Analysis of Variance; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchial Provocation Tests; Bronchoconstriction; Bronchoconstrictor Agents; Chi-Square Distribution; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Probability; Pulmonary Gas Exchange; Reference Values; Sensitivity and Specificity; Treatment Outcome

When treating bronchial hyperresponsiveness to so-called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time- and dose-dependent effects of 2 doses of fluticasone propionate (FP, 100 or 250 microg bid.) in improving exercise- (EIB) and methacholine-induced bronchoconstriction during 6 months of treatment, using a placebo-controlled parallel group study design. Thirty-seven children with asthma (aged 6 to 14 years; forced expired volume in 1 sec (FEV(1)) >/=70% predicted; EIB >/=20% fall in FEV(1) from baseline; no inhaled steroids during the past 4 months) participated in a double-blind, placebo-controlled, 3-arm parallel study. Children receiving placebo were re-randomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV(1) from baseline) and methacholine challenge using a dosimetric technique (expressed as PD(20)) were performed repeatedly during the study. During FP-treatment, the severity of EIB decreased significantly as compared to placebo within 3 weeks, the geometric mean % fall in FEV(1) being reduced from 34.1% to 9.9% for 100 microg FP bid, and from 35.9% to 7.6% for 250 microg FP bid (P < 0.05). These reductions in EIB did not differ between the 2 doses and were sustained throughout the treatment period. PD(20) methacholine improved significantly during the first 6 weeks as compared to placebo (P < 0.04) and steadily increased with time in both treatment limbs (P = 0.04), the difference in improvement between doses (100 microg FP bid, 1.6 dose steps; 250 microg FP bid, 3.3 dose steps) approaching significance after 24 weeks (P = 0.06). We conclude that in childhood asthma, the protection afforded by inhaled fluticasone propionate against methacholine-induced bronchoconstriction is time- and dose-dependent, whereas protection against EIB is not. This suggests different modes of action of inhaled steroids in protecting against these pharmacological and physiological stimuli. This has to be taken into account when monitoring asthma treatment.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Bronchoconstriction; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Male; Methacholine Chloride

In a prospective study, we investigated the long-term compliance to fluticasone propionate (FP) by dry powder inhalation (Rotadisk) in subjects with early signs of asthma and chronic obstructive pulmonary disease (COPD) without an established diagnosis. Subjects were selected from a large screening program on early stages of asthma and COPD (Detection, Intervention, and Monitoring Program of COPD and Asthma [DIMCA] program) in the general practice. Forty-eight adult subjects with "early signs of COPD" (slightly increased forced expiratory volume in 1 sec [FEV1] decline of >0.04L/year) and 29 adult subjects with "early signs of asthma" (signs of bronchial hyperresponsiveness or reversibility) participated in a randomized placebo-controlled trial with FP (Flixotide 500 microg daily) versus placebo with a duration of 2 years or 1 year, respectively. Compliance was measured by counting Rotadisks returned. By means of a questionnaire, participants were asked about perceived effects and/or side effects of the trial drug. The mean overall individual compliance rates of 72% (range 7%-102%) in the early COPD trial and 71% (range 8%-99%) in the early asthma trial were maintained throughout the study. Perceived effectiveness (12% of the participants) or side effects (30% of the participants) of the trial drug were not related to compliance. The willingness of patients to use the trial drug in daily practice if efficacy would be proved was statistically significantly related to compliance during the trial (p = 0.017). It was concluded that the compliance rates found were relatively high in patients with symptoms of mild asthma or COPD without an established diagnosis. Conviction of the importance of treatment influenced compliance more positively than perceived (side) effects. These results again emphasize the importance of patient education in establishing early treatment with inhaled corticosteroids.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Asthma; Double-Blind Method; Female; Fluticasone; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Nebulizers and Vaporizers; Patient Compliance; Powders; Time Factors

Many patients with persistent asthma need both long-acting bronchodilators and inhaled corticosteroids for optimal asthma control.. Our purpose was to compare the efficacy and safety of salmeterol 50 microg combined with fluticasone 100 microg (in a combination dry powder product) with that of placebo, fluticasone, or salmeterol alone.. A 12-week randomized, double-blind, multicenter study was conducted in 356 patients aged 12 years or older with asthma. After a 14-day screening period, patients were randomized to treatment with salmeterol 50 microg combined with fluticasone 100 microg (combination product), salmeterol 50 microg, fluticasone 100 microg, or placebo administered in the Diskus dry powder inhaler (GlaxoWellcome, UK) twice daily.. Mean change in FEV(1) at end point was significantly (P < or =.003) greater with the combination product (0.51 L) compared with placebo (0.01 L), salmeterol (0.11 L), and fluticasone (0.28 L). The combination product significantly increased (P < or =.013) area under the curve compared with placebo and fluticasone on day 1 and compared with placebo, salmeterol, and fluticasone at week 1 and week 12. Patients in the combination product group were less likely to withdraw from the study because of worsening asthma compared with those in the other groups (P < or =.020). The combination product significantly increased (P < or =.012) morning PEF (combination, 52.5 L/min; placebo, -23.7 L/min; salmeterol, -1.7 L/min; fluticasone, 17.3 L/min) and evening PEF at end point compared with the other groups. The combination product significantly (P < or =.025) reduced symptom scores and albuterol use compared with the other treatments and increased the percentage of nights with no awakenings and the percentage of days with no symptoms compared with placebo and salmeterol. All treatments were equally well tolerated.. Salmeterol 50 microg and fluticasone 100 microg combined in the Diskus powder delivery device offers significant clinical advantages over salmeterol or fluticasone alone at the same doses.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Powders; Salmeterol Xinafoate

Few studies have compared the efficacy of inhaled corticosteroids and leukotriene modifiers for the treatment of persistent asthma.. Our purpose was to compare the efficacy of a low dose of inhaled fluticasone propionate (FP) with that of oral zafirlukast in the treatment of persistent asthma previously treated with short-acting beta(2)-agonists alone.. A 12-week, randomized, double-blind, double-dummy, multicenter study was conducted in 451 patients aged 12 years and older with asthma who were symptomatic on short-acting beta(2)-agonists alone. After an 8- to 14-day run-in period, patients were randomized to treatment with FP 88 microg twice daily or zafirlukast 20 mg twice daily.. Treatment with FP was more effective than treatment with zafirlukast in increasing morning FEV(1) (by 0.42 L vs 0.20 L over baseline, P <.001), morning peak expiratory flow (by 49.94 L/min vs 11.68 L/min over baseline, P <. 001), and evening PEF (by 38.91 L/min vs 10.50 L/min over baseline, P <.001). Statistically significant differences between the two treatments in FEV(1) were noted after the first observation (week 4) and in morning and evening peak expiratory flow by week 2. Mean change in percentage of symptom-free days was greater with FP than with zafirlukast (28.5% of days vs 15.6% of days, P <.001) and FP significantly increased the percentage of rescue-free days by 40.4% of days compared with 24.2% of days with zafirlukast (P <.001). Treatment with FP significantly reduced albuterol use by 2.39 puffs per day compared with 1.45 puffs per day (P <.001) and increased the percentage of nights with no awakenings by 21.2% of nights compared with 8.0% of nights with zafirlukast (P <.001).. The clinical effectiveness of a low dose of FP as first-line therapy in patients with persistent asthma who are symptomatic on beta(2)-agonists alone is superior to that of zafirlukast.

Topics: Administration, Inhalation; Administration, Oral; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Dose-Response Relationship, Drug; Female; Fluticasone; Forced Expiratory Volume; Humans; Indoles; Male; Middle Aged; Phenylcarbamates; Sulfonamides; Therapeutic Equivalency; Tosyl Compounds

There are limited published data regarding the efficacy of once- versus twice-daily administration of flutica-sone propionate.. Our purpose was to evaluate the effectiveness of fluticasone propionate powder 200 microg/d administered as a once- or twice-daily dosage regimen in patients who were currently being treated with bronchodilators only (BD patients) and in patients who required inhaled corticosteroids for maintenance treatment of asthma (ICS patients).. Five hundred seventy patients were randomly assigned to receive one of the following inhaled treatments through the Diskus device (Glaxo Wellcome, Research Triangle Park, NC) for 12 weeks: fluticasone propionate 100 microg twice daily (FP100BID) or 200 microg once daily (FP200QD) or placebo.. BD patients treated with FP100BID, FP200QD, and placebo had mean increases in FEV(1) from baseline to end point of 0. 49 L, 0.37 L, and 0.21 L, respectively (P <.001, FP100BID vs placebo; P =.05, FP200QD vs placebo). ICS patients treated with FP100BID and FP200QD had mean increases in FEV(1) of 0.27 L and 0.11 L, respectively, compared with a decrease in FEV(1) of -0.08 L with placebo (P <.001, FP100BID vs placebo; P =.023, FP200QD vs placebo). BD patients treated with FP100BID and FP200QD had mean increases in morning peak expiratory flow from baseline to end point of 31 L/min and 27 L/min, respectively, compared with a 1 L/min increase in patients treated with placebo. ICS patients treated with FP100BID had a mean increase in morning peak expiratory flow (from baseline to end point) of 18 L/min compared with mean decreases of -3 L/min and -12 L/min in the FP200QD and placebo groups, respectively. More patients were withdrawn from placebo (26% and 48%, in BD and ICS patients, respectively) than from fluticasone propionate (7%-9% [BID-QD] and 18%-32% [BID-QD], in BD and ICS patients, respectively) because of failure to meet predetermined asthma stability criteria.. The efficacies of FP100BID and FP200QD were comparable with regard to improvement in pulmonary function and asthma stability in BD patients. In ICS patients, asthma control was maintained with FP200QD, whereas FP100BID provided greater improvements in pulmonary function and asthma stability.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Nebulizers and Vaporizers; Powders

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Female; Fluticasone; Humans; Interleukin-8; Male; Reference Values; Sensitivity and Specificity

This randomized, double-blind, double-dummy, multicentre cross-over study compared the effects on the hypothalamic-pituitary-adrenal (HPA) axis of fluticasone propionate (750 microg twice daily given via the Diskus) and budesonide (800 microg twice daily given via the Turbuhaler). Two treatment periods of 2 weeks each were preceded by a 2-week run-in period and separated by a 2-week washout period. During run-in and washout, patients received beclomethasone dipropionate (BDP) or budesonide at a constant dose of 1500-1600 microg day(-1). Sixty patients aged 18-75 years with moderate to severe asthma not fully controlled by treatment with 1500-1600 microg day(-1) budesonide or BDP entered run-in and 45 completed the study. HPA axis suppression was assessed by morning serum cortisol (area under the curve from 08.00 to 10.30 hours) and 12-h nocturnal urinary cortisol excretion, measured at the end of run-in (baseline 1), at the end of washout (baseline 2), and at the end of each treatment period. Neither budesonide nor fluticasone produced significant suppression of either parameter compared to baselines. Only a few patients had serum-cortisol and urinary cortisol values below the normal range, before and after treatment. This shows that the patients did not have adrenal suppression before entering the study. The ratio between the AUC serum cortisol measured after fluticasone treatment and after budesonide treatment was 0.99 (95% CI 0.92-1.06), indicating equivalent effects on the HPA axis. This result was achieved after having omitted two patients' results, due to their very sensitive reaction to budesonide, but not to fluticasone. Two exacerbations of acute asthma occurred during budesonide treatment and none during fluticasone treatment. Both treatments were well tolerated. In conclusion, budesonide 1600 microg day(-1) via Turbuhaler and fluticasone propionate 1500 microg day(-1) via Diskus had no clinical effects on the HPA axis in patients with moderate to severe asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Cross-Over Studies; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Pituitary-Adrenal System; Treatment Outcome

Changes in airway inflammation can be studied with bronchoalveolar lavage, but the widespread use of this procedure is limited by its invasiveness. The aim of this study was to evaluate the usefulness of induced sputum as a non-invasive alternative to bronchoalveolar lavage for studying changes in airway inflammation in patients with asthma. Thirty patients were treated for 12 weeks with an inhaled corticosteroid (fluticasone propionate (FP), 250 microg twice daily) or a short-acting beta-agonist (salbutamol (Sb), 400 microg twice daily) in a double-blind, double-dummy, randomized parallel group study. Sputum induction with hypertonic saline solution was performed twice before treatment and after 4, 8, 10, and 11 weeks of treatment. Bronchoalveolar lavage fluid divided into two pools (first 60 mL portion as bronchoalveolar lavage/bronchial wash (BAL/BW) and subsequent 80 mL as bronchoalveoalar lavage (BAL)) was obtained before and after 12 weeks of treatment. Changes in cell differentials and plasma-protein leakage (alpha2-macroglobulin, albumin, and their ratio (relative coefficient of excretion, RCE)) were analyzed in induced sputum and were compared with changes in BAL/BW and BAL. During treatment with FP, the PC20histamine (interpolated concentration of histamine that caused a fall in FEV1 of 20% of the baseline value) increased (P < .0001), and the percentage of eosinophils (P = .004), levels of (alpha2-macroglobulin (P = .09) and RCE (P = .007) decreased in sputum. These changes were different from those in the Sb group (PC20histamine P< .0001, eosinophils P= .004, alpha2-macroglobulin P= .003, RCE P = .01), in which alpha2-macroglobulin showed a significant increase (P = .015). Changes in the percentage of eosinophils and in the levels of alpha2-macroglobulin in sputum were associated with changes in the PC20histamine (Rs = -0.59, P = .007 and Rs = -0.47, P = .03, respectively). These correlations did not reach significance in BAL/BW and BAL fluid. The statistical power to detect changes in induced sputum was higher for the percentage of eosinophils and similar for plasma protein leakage as compared with analysis of BAL/BW and BAL fluid. We conclude that the analysis of induced sputum is a useful, non-invasive alternative to bronchoalveolar lavage for assessing the effects of antiinflammatory drugs in asthma.

Topics: Administration, Inhalation; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Blood Proteins; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Double-Blind Method; Eosinophils; Female; Fluticasone; Humans; Leukocyte Count; Male; Middle Aged; Saline Solution, Hypertonic; Sputum

This multi-national, double-blind, randomized, parallel-group study compared the efficacy and tolerability of fluticasone propionate 500 microg twice daily propelled either by the non-chlorofluorocarbon (CFC) propellant, hydrofluoroalkane (HFA) 134a, or the CFC propellants 11 and 12 used in the established pressurized metered dose inhaler (pMDI). The study period was 12 months and involved 412 subjects with moderate to severe asthma (HFA 134a pMDI: n = 203; CFC pMDI: n = 209). For the first 3 months, subjects kept a daily record card and attended the clinic every 4 weeks. Thereafter, they kept daily diaries for 2 weeks before each clinic assessment, which were performed at the end of 6, 9 and 12 months. Mean morning peak expiratory flow (PEF) increased during the first week in both treatment groups. By the end of week 12 the adjusted mean increase from baseline in morning PEF was 21 and 23 l min(-1) in the HFA 134a and CFC pMDI groups, respectively, and this increase was maintained throughout the 12-month study period. Similar improvements were detected in other diary card parameters and in clinic lung function measurements. The two groups were shown to be clinically equivalent in terms of all efficacy variables and there were no differences in tolerability. There were few reports of low serum cortisol levels during the 12-month study period, and serum cortisol levels were similar at baseline and after 12 weeks and 12 months of treatment in the two groups. In conclusion, the new HFA 134a fluticasone propionate pMDI is as effective and safe as the established CFC fluticasone propionate pMDI when used at a dosage of 1 mg day(-1).

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Chlorofluorocarbons; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate; Therapeutic Equivalency; Treatment Outcome

This study compared the efficacy and safety of the fluticasone propionate 125 microg pressurized metered dose inhaler (pMDI) propelled by either hydrofluoroalkane (HFA) 134a or chlorofluorocarbon (CFC) propellants, in adult patients with asthma. HFA 134a is a non-ozone depleting propellant used as a replacement for the CFC propellants 11 and 12 which are being phased out in accordance with the Montreal Protocol. Three hundred and eighty patients with mild to moderate asthma and 'room for improvement' in their treatment were randomized to receive fluticasone propionate 250 microg twice daily via pMDIs propelled by either CFC propellants 11 and 12 (n = 195) or HFA 134a (n = 185). Fluticasone propionate significantly improved lung function over the 4-week treatment period in both treatment groups. The improvement in mean morning peak expiratory flow (PEF) after 7 days of treatment was approximately 12 l min(-1) in both groups, rising to approximately 22 l min(-1) at the end of the 4-week treatment period. The adjusted mean difference between the two formulations over weeks 1-4 was -1 l min(-1) (90% confidence interval: -7, 5 l min(-1)), confirming their equivalence. Clinical comparability was also demonstrated with respect to secondary efficacy variables, including daily symptom scores, evening PEF and clinic visit expiratory measurements. There were no clinically relevant differences in adverse events or serum cortisol levels between the two groups. The fluticasone propionate 125 microg HFA 134a pMDI is an effective and well tolerated product and is a suitable replacement for the fluticasone propionate 125 microg CFC pMDI at a microgram equivalent dose.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Aged, 80 and over; Androstadienes; Anti-Asthmatic Agents; Asthma; Chlorofluorocarbons; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate; Therapeutic Equivalency; Treatment Outcome

A randomized, double-blind, cross-over study was conducted to assess the efficacy and safety of fluticasone propionate 1 mg twice daily administered via a pressurized metered dose inhaler (pMDI) containing the new non-chlorofluorocarbon (CFC) propellant (HFA 134a), or the established CFC propellants 11 and 12 in patients with severe asthma. The study comprised a 2-week run-in period followed by two 6-week treatment periods, with no washout period in between. One hundred and nineteen symptomatic adult patients with severe asthma, who were receiving inhaled beclomethasone 2-4 mg day(-1) or equivalent, were randomized to treatment. Patients were randomized to one of two sequence groups (sequence 1: HFA 134a pMDI then CFC pMDI or sequence 2: CFC pMDI then HFA 134a pMDI). The sequence groups differed with respect to mean peak expiratory flow (PEF) at baseline; however, the magnitude of the increase in PEF from baseline during treatment was similar in the two sequence groups. Mean PEF at baseline was 334 l min(-1) in sequence group 1 (HFA 134a-->CFC pMDI) and this increased to 357 l min(-1) and 366 l min(-1) during treatment with the HFA 134a and CFC pMDI, respectively. In sequence group 2 (CFC-->HFA 134a pMDI) mean PEF at baseline was 297 l min(-1) and this increased to 336 l min(-1) and 328 l min(-1) during treatment with the HFA 134a and CFC pMDI, respectively. Based on an overall analysis of the two treatment groups at week 6, equivalence was demonstrated; the mean treatment difference (HFA 134a-CFC pMDI) in morning PEF was 0 l min(-1) (90% confidence interval (CI), for difference between groups: -7, 6 l min(-1)). There was a comparable improvement in secondary efficacy variables, including clinic lung function measurements, in the two treatment groups. The incidence and type of most adverse events were similar in the two treatment groups. There was no difference in the adjusted geometric mean morning serum cortisol levels after treatment with the HFA 134a and CFC pMDI. Therefore, the fluticasone propionate HFA 134a pMDI constitutes a suitable replacement for the established CFC pMDI at a microgram equivalent dose.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Chlorofluorocarbons; Chronic Disease; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate; Therapeutic Equivalency; Treatment Outcome

The aim of this study was to compare the efficacy and safety in children of salmeterol (50 microg twice daily) plus fluticasone propionate (100 microg twice daily) when delivered together via a single Diskus inhaler (Seretide; combination therapy) or concurrently using two separate Diskus inhalers (concurrent therapy). In a multicenter, randomized, double-blind, double-dummy, parallel-group study, 257 children with reversible airways obstruction who remained symptomatic on inhaled corticosteroids (200-500 microg daily) alone were randomized to combination or concurrent therapy for 12 weeks. Efficacy was assessed by measuring daily peak expiratory flow (PEF), symptom scores, and rescue salbutamol use. In addition, lung function tests were performed at each clinic visit. Safety assessments included monitoring of adverse events and morning serum cortisol concentrations. The primary efficacy parameter (mean morning PEF) increased during treatment in both groups; adjusted mean changes were 33 and 28 L/min for the combination and concurrent therapies, respectively. The 90% confidence interval for the difference in mean morning PEF between treatment groups was within the +15 L/min criterion for clinical equivalence. Similarly, there were improvements in pulmonary function, symptom score, and rescue salbutamol use during treatment in both groups, with no significant differences between the combination and concurrent therapy groups for any of these secondary efficacy parameters. Both treatment regimens were well-tolerated and had comparable adverse event profiles. Mean morning serum cortisol levels increased similarly in both groups during the study. In conclusion, salmeterol and fluticasone propionate therapy given as a new combination product is as safe and effective in children with asthma as the same drugs given concurrently via separate inhalers.

Topics: Administration, Inhalation; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Nebulizers and Vaporizers; Salmeterol Xinafoate; Treatment Outcome

Three hundred and fifty-three asthmatic patients who remained symptomatic despite treatment with budesonide 800-1200 microg day(-1) (or equivalent) were randomized to a new combination therapy comprising salmeterol 50 microg and fluticasone propionate 250 microg (Seretide, Advair, Viani 50/250 microg) twice daily or budesonide 800 microg twice daily for 24 weeks. Patients kept daily records of their morning and evening peak expiratory flow (PEF), daytime and night-time symptom scores and daytime and night-time use of rescue salbutamol. Mean morning PEF increased by 451 min(-1) (baseline 361 l min(-1)) in the salmeterol/fluticasone propionate combination (SFC) group and by 19 l min(-1) (baseline 358 l min(-1)) in the budesonide group over the 24 weeks. The adjusted mean morning PEF over weeks 1 to 24 was significantly greater in the SFC group, despite the > three-fold lower corticosteroid dose (406 vs. 380 l min(-1); P < 0.001). A significantly greater improvement in evening PEF was also seen in the SFC group (adjusted mean 416 vs. 398 l min(-1); P<0.001). SFC also provided significantly better control of daytime symptoms and a significantly greater reduction in the requirement for rescue salbutamol compared with budesonide. These results demonstrate that SFC 50/250 microg twice daily is superior to budesonide 800 microg twice daily in the management of patients with moderate to severe asthma who are symptomatic on their existing dose of corticosteroid.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Treatment Outcome

Despite a good understanding of the disease and its treatments, asthma continues to place a large economic burden on healthcare systems. As such, it is important to consider the economic impact of alternative therapeutic options for the treatment of this condition to ensure that scarce resources are used in the most efficient manner possible. Thus, the aim of asthma management from an economic perspective is to reduce the burden of this disease through maximizing health gain with available resources. A prospective economic analysis was conducted as part of a multicentre, randomized, double-blind, comparative trial of salmeterol/fluticasone propionate combination product (SFC) 50/250 microg twice daily vs. budesonide (800 microg twice daily) in adults and adolescents with asthma who were symptomatic despite treatment with inhaled corticosteroids at doses of 800-1200 microg day(-1). Treatment effectiveness was measured in terms of successfully-treated weeks, defined as a > or =5% improvement in morning peak expiratory flow, episode-free days (a day without the need for rescue medication, no nocturnal awakening or adverse events) and symptom-free days. Cost-effectiveness analyses were performed using direct healthcare and drug costs, from the perspective of the Swedish healthcare system (1998 prices), with appropriate sensitivity analyses to test the robustness of the findings. Overall, SFC produced significantly higher (P<0.001) proportions of successfully-treated weeks, episode-free days and symptom-free days. Direct asthma management costs were similar between the two groups [SEK19.6 ($US2.4) for SFC vs. SEK18.5 (SUS2.2) for budesonide]. The cost per successfully-treated week was lower for SFC than for budesonide [SEK204 ($US24.8) vs. SEK300 ($US36.4) per week], as were the costs per episode-free day [SEK51.1 ($US6.2) vs. SEK75.1 ($US9.1) per day] and symptom-free day [SEK42.2 ($US5.1) vs. SEK53.0 ($US6.4) per day]. Incremental cost-effectiveness ratios showed that the additional costs to achieve additional benefits with SFC were minimal. Costs per additional successfully-treated week, symptom-free day and episode-free day with SFC were SEK31.6 ($US3.9), SEK9.2 ($US1.1) and SEK7.7 ($US0.9), respectively, relative to budesonide. Sensitivity analysis showed that the results were stable over a wide range of assumptions. The results suggest that SFC is a more cost-effective treatment than budesonide in the management of moderate to severe asthma.

Topics: Adult; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Cost-Benefit Analysis; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Prospective Studies; Treatment Outcome

This dose-ranging study evaluated the clinical efficacy and safety of inhaled fluticasone propionate administered once daily via a multidose powder inhaler in patients with moderate asthma (FEV(1), 45 to 75% predicted).. In this multicenter trial, 330 patients (> or = 12 years old) previously receiving inhaled corticosteroids or beta(2)-agonists alone were randomized in a double-blind manner to receive fluticasone propionate at 100, 200, or 500 microg once daily or matching placebo for 12 weeks.. Once-daily treatment with fluticasone propionate resulted in an improvement in efficacy variables, such as FEV(1), morning and evening peak expiratory flow (PEF), asthma symptom scores, nighttime awakenings, albuterol use, and duration of study participation. A dose-related trend was observed for improvements in morning and evening PEF and albuterol use. Statistical significance for pairwise comparisons was achieved for 200 microg and 500 microg fluticasone propionate vs placebo for all efficacy variables, and for 100 microg fluticasone propionate vs placebo for morning and evening PEF at most or all time points. Drug-related adverse events were few (< or = 5%) and mostly related to the topical effects of inhaled corticosteroids. No dose-response effect or clinically relevant differences were observed in morning plasma cortisol concentrations or after cosyntropin stimulation.. Once-daily treatment with fluticasone propionate was well tolerated and demonstrated some dose-related trends in improvements in lung function and asthma control in patients with moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Circadian Rhythm; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Powders; Safety; Severity of Illness Index

To evaluate the efficacy and safety of fluticasone propionate administered as a once-daily or twice-daily regimen over a period of 1 year to patients with moderate asthma.. Double-blind, randomized, parallel group, and placebo-controlled phase (12 weeks) and an open-label phase (54 weeks).. Multicenter study in an outpatient setting.. Patients (n = 253; age, > or = 12 years) with a mean FEV(1) of 67% predicted normal were stratified according to baseline therapy of maintenance inhaled corticosteroids vs beta(2)-agonists alone.. Fluticasone propionate (250 microg bid or 500 microg qd) or placebo (bid) was administered via the Diskus multidose powder inhaler (Glaxo Wellcome; Research Triangle Park, NC) for 12 weeks. During open-label treatment, patients were re-randomized to once-daily or twice-daily fluticasone propionate.. Compared to placebo, fluticasone propionate administered qd or bid significantly improved FEV(1) (p < 0.001), morning (p < 0.001) and evening peak expiratory flow (PEF; p < 0.001), asthma symptom scores (p < or = 0.001), and albuterol use (p

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Circadian Rhythm; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Powders; Safety; Severity of Illness Index

Inhaled corticosteroids are currently the cornerstone of asthma treatment. Some studies of high-dose fluticasone propionate in patients with no or mild asthma have, however, suggested substantial systemic absorption. We investigated the pharmacokinetics of fluticasone propionate in patients with asthma receiving appropriate doses for severity.. We did a double-blind, randomised, crossover study in 11 patients with asthma and 13 matched healthy controls (age 20-65 years; asthma patients forced expiratory volume in 1 s <75% and stable on high-dose inhaled corticosteroids). Patients received one 1000 microg intravenous dose or 1000 microg daily for 7 days inhaled (via spacer device) fluticasone propionate. In the 12 h after dosing, we monitored plasma fluticasone propionate and cortisol concentrations by mass spectrometry and competitive immunoassay with use of direct chemiluminescence. Analysis was by intention to treat.. After inhalation, geometric mean values were significantly lower in the asthma group than in controls for fluticasone propionate plasma area under curve (1082 [95% CI 850-1451] vs 2815 pg mL(-1) h(-1) [2262-3949], -62% difference [45-72]; p<0.001), maximum concentrations (117 [91-159] vs 383 pg/mL [302-546], -68% [-50 to -81]; p<0.001), and systemic bioavailability (10.1 [7.9-14.0] vs 21.4% [15.4-32.2], -54% [-27 to -70]; p=0.001). Intravenous-dose clearance, volume of distribution at steady state, plasma half-life, and mean residence time, were similar in the two groups. Less suppression of plasma cortisol concentrations was seen in the asthma group than in controls 4-12 h after inhaled fluticasone propionate.. Systemic availability of fluticasone propionate is substantially less in patients with moderate to severe asthma than in healthy controls. Inhaled corticosteroids that are absorbed through the lungs need to be assessed in patients who are receiving doses appropriate for disease severity, and not in normal volunteers.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Area Under Curve; Asthma; Biological Availability; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Middle Aged; Respiratory Mechanics

Inhaled corticosteroids are effective in the treatment of children with asthma. It is uncertain how inhaled corticosteroids compare with oral corticosteroids in the management of severe acute disease.. We performed a double-blind, randomized trial involving 100 children five years of age or older who had severe acute asthma (indicated by a forced expiratory volume in one second [FEV1] that was less than 60 percent of the predicted value) and in whom the results could be evaluated. All were treated with an aggressive bronchodilator regimen and received one dose of either 2 mg of inhaled fluticasone through a metered-dose inhaler with a spacer or 2 mg of oral prednisone per kilogram of body weight. They were assessed hourly for up to four hours.. The mean (+/-SD) base-line FEV1 as a percentage of the predicted value was 46.3+/-12.5 in the fluticasone group (51 subjects) and 43.9+/-9.9 in the prednisone group (49 subjects). The FEV1 increased by a mean of 9.4+/-12.5 percentage points in the fluticasone group and by 18.9+/-9.8 percentage points in the prednisone group four hours after therapy (P< 0.001). None of the children in the prednisone group had a reduction in FEV1 as a percentage of the predicted value from base line to four hours, as compared with 25 percent of those in the fluticasone group (P<0.001). Sixteen (31 percent) of the children treated with fluticasone were hospitalized, as compared with five (10 percent) of those treated with prednisone (P=0.01).. Children with severe acute asthma should be treated with oral prednisone and not with inhaled fluticasone or a similar inhaled corticosteroid.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Hospitalization; Humans; Male; Prednisone; Pulmonary Ventilation

It has been reported that intranasal corticosteroids can influence bronchial hyperresponsiveness (BHR) in asthmatic subjects with seasonal rhinitis. The purpose of the present study was to evaluate the effect of intranasal fluticasone propionate and beclomethasone dipropionate on BHR and bronchial calibre (forced expiratory volume in one second, FEV(1)) in children and young adults with seasonal rhinitis and mild asthma during two consecutive grass pollen seasons.. In the first pollen season 25 patients aged 8-28 years were included in a double blind, placebo controlled study. The active treatment group used fluticasone aqueous spray 200 microgram once daily. In the second pollen season 72 patients aged 8-28 years participated in a double blind, placebo controlled study of a similar design to that of the previous year except that an additional treatment group of patients using beclomethasone 200 microg twice daily was included. FEV(1) was measured before and after three and six weeks of treatment; BHR to methacholine (PD(20)) was measured before and after six weeks of treatment.. In the first season the mean (SD) logPD(20) of the patients decreased significantly both in the fluticasone group (from 2.43 (0.8) microgram to 1.86 (0.85) microgram) and in the placebo group (from 2.41 (0.42) microgram to 1.87 (0.78) microgram) without any intergroup difference in the change in logPD(20). In the second pollen season the mean logPD(20) in the fluticasone, beclomethasone, and placebo groups did not change significantly.. Intranasal steroids did not influence BHR during two grass pollen seasons in children and young adults with seasonal rhinitis and mild asthma.

Topics: Administration, Intranasal; Adolescent; Adult; Allergens; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Patient Compliance; Pollen; Rhinitis, Allergic, Seasonal; Treatment Outcome

To analyse correlation between bronchial hypersensitivity in bronchial asthma (BA) and environmental factors; to propose methods of relevant correction.. The trial included 97 BA patients (42 males, 55 females) aged 17-79 years. Bronchial sensitivity was studied by means of dose-dependent bronchial resistance curve (Rrs) plotted by the unit Masterlab (Germany) in the course of long-term inhalation of a gradually rising dose of methacholine. A regression analysis was made of the dependence of fluticasone bipropionate effectiveness on clinical symptoms of the disease.. Bronchial hypersensitivity depends on initial clinical symptoms of BA, in a less degree on bronchial permeability, severity of inflammation of bronchial mucosa.. Local corticosteroid fluticasone propionate is a drug of choice in the treatment of mild and moderate BA.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Airway Resistance; Androstadienes; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Female; Fluticasone; Humans; Male; Methacholine Chloride; Middle Aged; Regression Analysis; Severity of Illness Index

Prolonged treatment with inhaled steroids is recommended for long-term control of asthma in children; however, it can interfere with growth and body composition.. The aim of this study is to answer the question whether 6 months treatment with inhaled steroids causes body fat accumulation and growth velocity reduction.. Hospital-based, open study of body composition [by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA) and skinfolds] and growth of 26 asthmatic children, treated for 6 months with inhaled steroids [budesonide (BUD) 400 microg/day (group 1) or fluticasone proprionate (FP) 200 microg/day (group 2)], sodium cromoglycate and beta2-agonist (salbutamol) compared with a control group of 16 asthmatic children treated only with sodium cromoglycate and beta2-agonist.. On average, total and regional fat mass, adjusted for pubertal stage and gender, and growth velocity were similar in all three groups of patients and were not influenced by treatment (% mean change +/- 1 SD of fat mass during treatment in BUD 0.1 +/- 3.0%, FP -1.1 +/- 3%, and control -2.8 +/- 3.5%; ANOVA P > or = .05); however seven patients, two in group 1 (1 preschool child), three in group 2 (2 preschool children) and two in the control group (two prepubertal boys aged 8.5 and 9.5 year), during treatment, showed a growth velocity standard deviation score below the third percentile.. A 6-month treatment with inhaled BUD and FP does not induce body fat accumulation; however, in a few preschool children the treatment was associated with growth velocity below the third percentile. Our results suggest the need for constant monitoring of growth in all asthmatic children on chronic treatment with inhaled steroids. Further studies devoted to the effects of inhaled steroids use in preschool children are needed.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenergic beta-Agonists; Androstadienes; Anthropometry; Anti-Inflammatory Agents; Asthma; Body Composition; Budesonide; Child; Child, Preschool; Cromolyn Sodium; Female; Fluticasone; Glucocorticoids; Growth; Humans; Male; Skinfold Thickness

(1) To establish recruitment rates of newly presenting asthmatic children. (2) To establish acceptability of study protocols. (3) To pilot age-specific quality of life (QoL) assessment. (4) To assess short-term (6 months) outcomes of inhaled corticosteroids (ICS) treatment. (5) To refine sample size calculations for a definitive study.. A randomised pragmatic longitudinal trial design was used, with no blinding or placebo, to examine early ICS introduction similar to its use in practice. Subjects were assessed at entry, 3 and 6 months.. Subjects were recruited from six general practices. Children under 6 years were assessed at the Craig Research and Investigation Unit, Royal Aberdeen Children's Hospital, or their family home, and subjects 6 years and over were assessed at their general practice.. Children (aged 6 months-16 years) with symptoms suggestive of asthma/wheeze that had commenced no longer than 12 months before were identified retrospectively and prospectively from general practices. Subjects were also required to be naïve to prophylactic therapy with no other lung disease/concomitant illness.. Subjects were randomised to ss2-agonist (ss2-only group) or ss2-agonist and ICS (ICS group) for 6 months. Physicians could later prescribe ICS in controls if needed.. (1) Pulmonary function. (2) Asthma symptom diary. (3) Symptomatic health status questionnaire. (4) Caregiver's and child's QoL. (5) Growth. (6) Bone mass. (7) Bone turnover. (8) Economic issues.. Of over 15,000 children yielded from general practice records, 11% had symptoms suggestive of asthma/wheeze, and two-thirds of these already used ICS. Of the remaining, 141 subjects met the criterion of early asthma, and 86 were randomised. Two-thirds of those randomised were < 6 years old, the males:females ratio was 2:1, and 67% had a family history of atopy. RESULTS - PHYSIOLOGICAL DEVELOPMENT: Pulmonary function did not significantly improve in the older children. Although tidal breathing measures in the pre-school children were significantly higher at 6 months in the ss2-only group, there was great variability. Incidence of wheeze and night-time cough reduced equally in both groups. Reduction of night-time symptom score and reliever use, and increase in symptom-free days were only significant in the ss2-only group. No significant differences were found in growth and bone mass between the two groups, but bone metabolism was significantly reduced at 6 months in the ICS group. RESULTS - PSYCHOLOGICAL DEVELOPMENT: The caregiver's QoL questionnaire was sensitive to child symptom changes over 3 months, but absolute impact of child symptoms on their QoL varied, whereas the child-centred questionnaire was not sensitive to change. RESULTS - ECONOMICS: There were no significant differences in medical consultation costs between the groups, but, as expected, prescription costs in the ICS group were higher over 6 months. Combined healthcare costs were significantly higher for patients assigned to ICS, but there were no significant differences in any effectiveness measures between the groups.. Most (96%) of the proposed sample was recruited, and the low drop-out rate (8%) demonstrated acceptability of the study protocol. Most children first presenting with symptoms suggestive of asthma were < 6 years old and represented a group biased towards mild to moderate asthma, or virally induced wheeze. The caregiver's QoL questionnaire was found to better reflect a child's symptom changes than a child-centred instrument. In the short term, no adverse effects were seen on growth, but ICS treatment significantly reduced bone metabolism. Most of the young children with asthma/wheeze improved over time with ss2-agonist treatment alone, and clinical benefits of early ICS intervention amongst these children were not detected; however, there was inadequate power in this pilot study to establish this. (AB

Topics: Adolescent; Androstadienes; Anthropometry; Anti-Asthmatic Agents; Asthma; Bone and Bones; Bone Density; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Cost-Benefit Analysis; Female; Fluticasone; Health Care Costs; Humans; Infant; Longitudinal Studies; Male; Pilot Projects; Quality of Life; Regression Analysis; Respiratory Function Tests; Statistics, Nonparametric; Surveys and Questionnaires; Treatment Outcome; United Kingdom

Flovent Diskus is a powder formulation of the inhaled corticosteroid fluticasone propionate (FP) delivered via a breath-actuated, multidose inhaler.. To determine the efficacy and safety of dry powder FP administered once or twice daily (200 microg per day) to children with persistent asthma.. Twelve-week, randomized, double-blind, placebo-controlled, multicenter trial with a 52-week, open-label extension. Children aged 4 to 11 were required to have pulmonary function 50% to 85% of predicted values. The population was stratified for baseline therapy (inhaled corticosteroid/cromolyn or bronchodilators only). After a 2-week placebo run-in, 242 patients received dry powder FP 200 microg each morning, dry powder FP 100 microg BID, or placebo for 12 weeks; 192 were rerandomized to the QD or BID regimen for an additional 52 weeks of open-label treatment. Primary endpoints were mean changes in FEV1 and morning PEF recorded at clinic visits.. Both dry powder FP regimens significantly improved FEV1, evening PEF, and asthma symptoms at the double-blind phase endpoint (P < or = .017 compared with placebo). The BID regimen also significantly improved morning PEF and nighttime awakenings due to asthma (P < or = .005). Among patients previously treated with inhaled corticosteroids/cromolyn, improvements observed with the QD and BID regimens were similar. Patients switched from BID to open-label QD treatment showed additional improvements at week 52 generally comparable to patients who received the BID regimen during both phases. Fluticasone propionate was well tolerated for up to 64 weeks with few reports of drug-related adverse events or morning plasma cortisol abnormalities.. Once daily dosing of dry powder FP 200 microg is an effective and convenient alternative for children whose asthma is controlled with a more frequent dosing regimen of inhaled corticosteroids.

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Powders; Therapeutic Equivalency

Inhaled corticosteroids have become the mainstay treatment of bronchial asthma. However, simultaneous evaluations of efficacy and side effects are few. This study aimed to compare the relative effect of fluticasone propionate (FP) and budesonide (BUD) on bronchial responsiveness and endogenous cortisol secretion in adults with asthma. The study was double-blind and included 66 adults with asthma, who were randomized to FP (n = 33) or BUD (n = 33). Prestudy, all participants were clinically stable, using inhaled corticosteroids and hyperresponsive to methacholine. Eligible patients were randomized to three consecutive 2-wk periods with either FP 250 microg twice daily, FP 500 microg twice daily, and FP 1,000 microg twice daily, or BUD 400 microg twice daily, BUD 800 microg twice daily, and BUD 1,600 microg twice daily, delivered by Diskhaler and Turbuhaler, respectively. Before randomization and at the end of each treatment, bronchial methacholine PD(20), 24-h urinary cortisol excretion (24-h UC), plasma cortisol, serum osteocalcin, and blood eosinophils were determined. The relative PD(20) potency between FP and BUD was 2.51 (95% CI, 1.05-5.99; p < 0. 05), while the relative 24-h UC potency was 0.60 (95% CI, 0.44-0.83; p < 0.01). The differential therapeutic ratio (FP/BUD) based on PD(20) potency and 24-h UC was 4.18 (95% CI, 1.16-15.03; p < 0.05). The difference in systemic potency was also seen for plasma cortisol, serum osteocalcin, and blood eosinophils. Therapeutic ratio over a wide dose range, determined by impact on bronchial responsiveness and endogenous corticosteroid production, seems to favor FP.

Topics: Administration, Inhalation; Adrenal Cortex; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Male; Time Factors

Asthma is a disease of chronic inflammation and bronchoconstriction. Inhaled corticosteroids (ICSs) provide important anti-inflammatory treatment but may not provide optimal control of asthma when taken alone. Two therapeutic alternatives for enhanced asthma control are to substitute the combination of fluticasone propionate (FP) and salmeterol (FP/Salm Combo) through the Diskus inhaler or to add montelukast to existing ICS therapy.. We compared the efficacy and safety of FP/Salm Combo through the Diskus inhaler versus montelukast added to FP (FP + montelukast) in patients whose symptoms were suboptimally controlled with ICS therapy.. We performed a multicenter, double-blind, double-dummy, parallel-group, 12-week study in 447 patients with asthma who were symptomatic at baseline while receiving low-dose FP. Patients were treated for 12 weeks with one of the following: (1) combination of FP 100 microg plus salmeterol 50 microg twice daily through the Diskus inhaler, or (2) FP 100 microg twice daily through the Diskus inhaler plus oral montelukast 10 mg once daily.. FP/Salm Combo treatment provided better overall asthma control than FP + montelukast with significantly greater improvements in morning peak expiratory flow (+24.9 L/min vs +13.0 L/min, P <.001), evening peak expiratory flow (+18.9 L/min vs +9.6 L/min, P <.001), and forced expiratory volume in 1 second (+0.34 L vs +0.20 L, P <.001), as well as a change in the percentage of days with no albuterol use (+26.3% vs +19.1%, P =.032) and the shortness of breath symptom score (-0.56 vs -0.40, P =.017). The groups had comparable improvements in chest tightness, wheeze, and overall symptom scores. Asthma exacerbation rates were significantly lower (P =.031) in the FP/Salm Combo group (4 patients, 2%) than in the FP + montelukast group (13 patients, 6%). Adverse event profiles were comparable.. Symptomatic patients on low-dose ICS therapy had significantly greater improvement in asthma control when switched to the FP/Salm Combo than when montelukast was added to ICS therapy.

Topics: Acetates; Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Asthma; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Patient Compliance; Quinolines; Salmeterol Xinafoate; Sulfides

To investigate the potential for mometasone furoate (MF) to exert systemic effects following administration by dry powder inhaler (DPI) or metered-dose inhaler (MDI).. Three randomized, evaluator-blind, placebo-controlled, parallel-group, 28-day studies.. Adults with mild-to-moderate persistent asthma.. Study 1 (12 patients per treatment group; MF DPI at 200 microg bid, 400 microg qd, 800 microg qd, or 1,200 microg qd). Study 2 (16 patients per treatment group; MF DPI at 400 microg bid or 800 microg bid, or oral prednisone at 10 mg qd). Study 3 (16 patients per treatment group; MF MDI at 400 microg bid or 800 microg bid, or fluticasone propionate [FP] at 880 microg bid by MDI).. Study 1. Plasma concentrations were near the lower limit of quantitation (50 pg/mL) at the MF DPI 400-microg qd dosage and approximately 250 pg/mL at the 1,200-microg qd dosage. The area under the curve for serum cortisol concentrations over 24 h (AUC(24)) was essentially unaltered at all doses. Study 2. Plasma levels over days 7 to 28 were 100.3 +/- 5.9 pg/mL (mean +/- SEM) for MF DPI 400 microg bid, and 181.0 +/- 10.9 pg/mL for 800 microg bid. Although there were relatively low levels of suppression (19 to 25%) at earlier time points for MF DPI 400 microg bid, serum cortisol AUC(24) levels at day 28 were similar to placebo. MF DPI 800 microg bid and oral prednisone both decreased serum cortisol AUC(24) levels at days 7 to 28 by 28.0 +/- 8.3% and 67.2 +/- 3.6%, respectively. The response to cosyntropin was normal in 15, 14, 11, and 1 of the patients in the placebo, MF DPI 400 microg bid, MF DPI 800 microg bid, and prednisone groups, respectively. Study 3. MF MDI caused even less systemic exposure than by DPI. MF MDI 800 microg bid (24.0 +/- 3.1%) and FP (51.7 +/- 3.8%) caused a significant decrease in serum cortisol AUC(24) on days 14 to 28. MF MDI 400 microg bid was similar to placebo treatment at all time points.. The MF 800-microg bid dosage (1,600 microg/d), which is twice the highest projected clinical dosage, represents the lower limit for consistently detectable systemic effects of MF.

Topics: Administration, Inhalation; Administration, Oral; Administration, Topical; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Area Under Curve; Asthma; Cosyntropin; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Mometasone Furoate; Pituitary-Adrenal System; Prednisone; Pregnadienediols

The aim of these studies was to compare the pharmacokinetics of inhaled fluticasone propionate (FP) after repeated administration via the Diskus or Diskhaler dry powder inhalers (DPIs) to patients with mild-to-moderate asthma.. Both studies evaluated the pharmacokinetics of inhaled administration of FP via a DPI to patients with mild-to-moderate asthma, according to a randomised, double-blind, placebo-controlled design. In the first study, FP 100 microg or 500 microg was administered twice daily via the Diskhaler for 6 weeks and, in the second, FP 500 microg was administered via the Diskus or Diskhaler for 12 weeks.. In the first study, plasma FP concentrations could be detected consistently only with the higher dose; the lower dose produced concentrations close to or below the 0.025 microg/L quantification limit of the radioimmunoassay used. From detailed analysis of a subgroup of patients receiving the 500 microg dosage, steady-state plasma FP concentrations were attained within one week of commencing treatment. After 4 weeks, the maximum plasma FP concentration (Cmax) in this subgroup was 0.096 microg/L [95% confidence interval (CI) 0.066-0.141] and the area under the plasma FP concentration-time curve up to the last quantifiable concentration (AUClast) was 0.491 microg/L x h (95% CI: 0.256-0.940). The steady-state to single dose accumulation ratio for FP after twice-daily administration varied between patients: a ratio of approximately 1.7 was recorded after comparison of Cmax at week 4 and day 1. In the second study, the point estimate of the Diskus to Diskhaler ratio for Cmax in all patients was 0.91 (90% CI: 0.76-1.10) after 4 weeks' treatment. From a detailed analysis of a subgroup of patients, the corresponding ratio for AUClast at the same time point was 1.15 (90% CI: 0.69-1.94), indicating no significant difference in systemic exposure to FP between the 2 devices. Steady-state kinetics were achieved by week 1: the point estimate ratios of Cmax and AUClast at week 4 compared with week 1 were 0.88 (90% CI: 0.66-1.16) and 0.95 (90% CI: 0.66-1.36), respectively. Administration of FP via either DPI had no effect on plasma cortisol levels over the 12-hour postdose period.. In patients with asthma receiving repeated inhaled doses of FP, the systemic exposure (AUC) after inhalation from the Diskus was similar to that from the Diskhaler, with no difference between the DPIs in the effects on cortisol suppression. The 2 DPIs therefore have very similar pharmacokinetic profiles.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Area Under Curve; Asthma; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Powders

The aim of this analysis was to compare the systemic exposure to inhaled fluticasone propionate (FP) after administration of either single or repeated dose regimens via dry powder and metered-dose inhalers in patients with asthma and healthy volunteers.. The pharmacokinetics of FP, a topically active glucocorticoid administered by inhalation for the treatment of asthma and rhinitis, are well characterised in healthy volunteers. As asthma is characterised by pathophysiological changes in the lung, it may be inappropriate to use data from studies in healthy volunteers to predict the deposition and absorption of FP in patients with asthma.. Pooled data from 13 pharmacokinetic studies showed that the systemic availability of FP (measured as area under the plasma FP concentration-time curve) after single or multiple administration by inhalation was 2 to 3 times lower in patients with asthma than in healthy volunteers. This observation correlated well with the systemic effects of FP in the 2 groups. Reduction in 24-hour urinary cortisol excretion after inhalation of FP (determined in 9 of the studies) was greater in healthy volunteers than in patients with asthma. The hypothalamic-pituitary-adrenal axis suppression caused by systemic exposure to FP in adults with asthma is therefore substantially less than that in healthy volunteers.. Differences in the deposition of FP in the lungs of patients with asthma, probably caused by obstructed inspiratory airflow, may explain this observation.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Area Under Curve; Asthma; Female; Fluticasone; Humans; Hydrocortisone; Male; Middle Aged; Powders

The aim of the present study was to investigate the efficacy and safety of nebulized fluticasone propionate (FP Nebules) compared with oral soluble prednisolone in children with an acute exacerbation of asthma. The study used an international, multi-centre, randomized, double-blind, parallel group design. Three hundred and twenty-one patients, aged 4-16 years old, who presented with an acute exacerbation of asthma, were randomly allocated to either nebulized FP (1 mg b.d.) or oral prednisolone (2 mg kg(-1) day(-1) for 4 days then 1 mg kg(-1) day(-1) for 3 days) for 7 days. Patients in the FP group showed a significantly greater increase in diary card morning peak expiratory flow (PEF) over 7 days compared with patients in the prednisolone group (difference = 9.51 min(-1), CI = 2.1, 16.8, P = 0.034). Similar increases for both treatments were shown for evening PEF. Clinic PEF improved with both treatments, but was significantly greater in patients taking FP after 7 days (difference = 11.41 min(-1), CI = 2.8, 20.0, P = 0.029). Both treatments reduced symptom scores to a similar extent. The two treatments were well tolerated, and there was no difference in the incidence of adverse events. The present study demonstrated that nebulized FP is at least as effective as oral prednisolone in the treatment of children presenting with an acute exacerbation of asthma.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Adolescent; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Humans; Male; Peak Expiratory Flow Rate; Prednisolone; Treatment Outcome

Steroid therapy is the third most common cause of osteoporosis, after loss of gonad function and senescence. The aim of the present study was to evaluate the protective action of clodronate on bone mass loss induced by steroid therapy. Sixty patients with bronchial asthma receiving either fluticasone (250 mg x 4/day) or beclomethasone (250 mg x 4/day) inhaled corticosteroid treatment were enrolled. Half the patients received combination treatment with clodronate (100 mg i.m./14 days), for a total period of 12 months. All patients were evaluated at baseline and at the end of treatment for bone mineral density (BMD) and calcium/phosphor metabolism parameters (kalemia, kaluria, phosphoremia, phosphaturia, alkaline phosphatase and hydroxyprolinuria over a 24-h period). The results of this preliminary study confirm the protective influence of clodronate on bone mass loss, as documented by the increment in mean values in BMD reported at the end of treatment compared with baseline values.

Topics: Administration, Inhalation; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bone Density; Chronic Disease; Clodronic Acid; Fluticasone; Humans; Infusion Pumps; Male; Middle Aged; Osteoporosis

Many patients with severe asthma are dependent on oral corticosteroids for maintenance control of their disease. Treatments that allow patients to be weaned off oral corticosteroids may help to minimize the risk of side effects associated with their chronic use.. This study evaluated whether inhaled fluticasone propionate powder could maintain pulmonary function while reducing the dose of oral prednisone in patients with chronic, severe asthma.. Oral prednisone-dependent (5 to 40 mg/day) adolescents and adults with asthma (n = 111; mean FEV1 = 61% of predicted value) were randomized to placebo or twice daily fluticasone propionate 500 or 1000 microg administered by means of a multidose powder inhaler for 16 weeks in a double-blind, parallel-group study. Patients underwent controlled prednisone reduction on the basis of predetermined asthma stability criteria.. Oral prednisone was eliminated by 75% and 89% of patients in the twice daily 500 and 1000 microg fluticasone propionate groups, respectively, versus 9% of the placebo group (P <.001). FEV1, morning and evening peak expiratory flow, asthma symptoms, albuterol use, and nighttime awakenings improved with fluticasone propionate treatment, achieving statistical significance (P

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Placebos; Powders; Prednisone; Quality of Life

The current stepwise approach to pharmacotherapy in the treatment of asthma includes the initiation of an inhaled corticosteroid with the addition of a long-acting inhaled bronchodilator if low dose inhaled corticosteroid fails to control asthma symptoms.. To determine whether initiation of salmeterol and fluticasone propionate treatment together improves asthma control greater than initiation of monotherapy with the individual agents alone with no additional safety risk in patients with asthma who had not previously been treated with inhaled corticosteroids.. A total of 136 male and female patients at least 12 years of age with asthma [forced expiratory volume in 1 second (FEV) between 50% and 80% of predicted] were randomized to twice daily salmeterol 42 microg, fluticasone propionate 88 microg, fluticasone propionate 220 microg, salmeterol 42 microg plus fluticasone propionate 88 microg, salmeterol 42 microg plus fluticasone propionate 220 microg, or placebo for 4 weeks.. Patients treated with salmeterol combined with fluticasone propionate had improvements over baseline in FEV at endpoint that were at least twice as great (0.6 to 0.7 L) as improvements in patients treated with salmeterol (0.3 L) or fluticasone propionate alone (0.3 L) (P < .05). Patient-rated data (peak expiratory flow, asthma symptom scores, percent of days with no asthma symptoms) confirmed greater (P < .05) mean change from baseline improvements after combined treatment compared with fluticasone propionate alone. No clinically significant differences were noted between treatment groups in any safety measurement.. Initiation of maintenance therapy with salmeterol and fluticasone propionate in patients with asthma treated with short-acting beta2-agonists alone provides greater improvements in pulmonary function and symptom control than initiation of maintenance therapy with fluticasone propionate alone.

Topics: Adolescent; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Arrhythmias, Cardiac; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Electrocardiography; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Pilot Projects; Safety; Salmeterol Xinafoate; Severity of Illness Index; Treatment Outcome

Fluticasone propionate is a topically active glucocorticoid with potent antiinflammatory activity in the treatment of asthma.. This study evaluated the safety and efficacy of fluticasone propionate administered via the Diskus and Diskhaler powder delivery devices in subjects with mild-to-moderate asthma.. Fluticasone propionate (500 microg twice daily) or placebo was administered via the Diskus and Diskhaler to 213 adolescent and adult asthma subjects in a randomized, double-blind, double-dummy, parallel-group study for 12 weeks. Subjects were stratified according to baseline therapy of inhaled corticosteroids or beta2-agonists alone. Subjects were dropped from the study if they met predefined criteria for lack of efficacy.. Fluticasone propionate improved pulmonary function both in subjects previously treated with inhaled corticosteroids or beta2-agonists alone. At endpoint, fluticasone propionate significantly improved forced expiratory volume in 1 second (P < .001), morning and evening peak expiratory flow (P < .001), and asthma symptom scores (P < or = .016), and significantly reduced nighttime awakenings (P = .016; Diskhaler group only) and rescue albuterol use (P < .001). Overall, efficacy measurements for the Diskus and Diskhaler were similar. More placebo-treated subjects (34%) withdrew from the study due to lack of efficacy than subjects in the Diskus (5%) or Diskhaler (5%) groups. The incidence and severity of adverse events were similar across groups. Measurement of plasma fluticasone propionate and cortisol concentrations showed no apparent influence of device on systemic exposure.. Fluticasone propionate powder, administered via the Diskus or Diskhaler inhalation devices, was well tolerated and effective in the treatment of mild-to-moderate persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Packaging; Drug Therapy, Combination; Equipment Design; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Nebulizers and Vaporizers; Patient Dropouts; Peak Expiratory Flow Rate; Pituitary-Adrenal System; Powders; Safety; Severity of Illness Index; Treatment Outcome

To compare the efficacy and adverse effects of inhaled fluticasone propionate (FP), 400 microgram/d, with those of budesonide (BUD), 800 microgram/d, in children with moderate to severe asthma.. Three hundred thirty-three children, ages 4 to 12 years, receiving inhaled corticosteroids were enrolled in a double-blind, double-dummy, randomized, parallel-group study. After a 2-week run-in phase, 166 children received FP and 167 received BUD for 20 weeks. The primary outcome variable was mean morning peak expiratory flow; the 2 treatments were to be regarded as equivalent if the 90% CI for the treatment difference was within +/- 15 L/min. Pulmonary function, height, and diary cards were assessed at each visit; and morning serum cortisol levels were determined before and after treatment.. Baseline peak expiratory flow was similar, FP 236 +/- 72 (SD) L/min and BUD 229 +/- 74, increasing after treatment to 277 +/- 41 and 257 +/- 28, a difference between treatments of 12 L/min (90% CI 6-19 L/min; P =.002). Symptom control and use of rescue medication were the same. Cortisol levels after treatment were 199 nmol/L (FP) and 183 nmol/L (BUD) (treatment ratio = 1.09; 90% CI 0.98-1.21; P =.172). Linear growth was less in those receiving BUD (mean difference, 6.2 mm; 95% CI 2.9-9.6; P =.0003).. FP at half the dose was superior to BUD in improving peak expiratory flow and comparable in controlling symptoms. Growth was reduced with BUD compared with FP, but there was no difference in serum cortisol suppression or hepatic or renal function.

Topics: Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Peak Expiratory Flow Rate; Respiratory Function Tests; Severity of Illness Index

Many clinicians are reluctant to prescribe inhaled corticosteroids because of concerns over potential effects on the hypothalamic-pituitary-adrenal axis.. The purpose of this study was to compare the adrenal responses to 6-hour cosyntropin infusion after treatment with fluticasone propionate aerosol, triamcinolone acetonide aerosol, prednisone, and placebo for 4 weeks, a sufficient time interval to assess any effects on the adrenal response to stress.. This double-blind, triple-dummy, randomized, placebo-controlled study was conducted in 128 patients to evaluate adrenal response to 6-hour cosyntropin infusion (a clinically relevant method for evaluating adrenal function) after 28 days of treatment with fluticasone propionate aerosol 88 microg or 220 microg twice daily, triamcinolone acetonide aerosol 200 microg 4 times daily or 400 microg twice daily, prednisone 10 mg once daily, and placebo.. After 28 days of treatment, mean plasma cortisol response to cosyntropin over 12 hours after initiation of the 6-hour infusion was similar among fluticasone, triamcinolone, and placebo groups; cortisol response was significantly (P <.05) reduced after treatment with prednisone compared with the other treatment groups. Mean 8-hour area under the plasma cortisol concentration-time curves and peak plasma cortisol concentrations were significantly (P

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Cosyntropin; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Prednisone; Time Factors; Triamcinolone Acetonide

Two multicenter, randomized, double-masked, placebo-controlled, parallel-group studies were conducted in adult patients with mild-to-moderate persistent asthma to assess the effects of 4 weeks of treatment with inhaled corticosteroids on hypothalamic-pituitary-adrenal (HPA) axis function. The first study compared fluticasone propionate 100 and 500 microg twice daily, triamcinolone acetonide 300 and 500 microg twice daily, oral prednisone 10 mg every morning, and placebo. The second study compared fluticasone propionate 100 and 250 microg twice daily, flunisolide 500 microg twice daily, and placebo. Therapeutic doses of fluticasone propionate, triamcinolone acetonide, and flunisolide were found to be comparable to each other and to placebo in their lack of adrenal suppressive effects, based on mean plasma cortisol responses to 6-hour cosyntropin infusion. Prednisone produced significantly greater suppression of HPA-axis function than did any of the inhaled corticosteroids or placebo (P<0.001). Mean reductions from baseline in 8-hour area under the plasma concentration-time curve (AUC) and 8-hour peak plasma cortisol concentrations and the mean percentage of change from baseline in 8-hour AUC were significantly greater after treatment with triamcinolone acetonide 500 microg twice daily compared with placebo (P< or =0.042). These findings indicate that fluticasone propionate has no greater systemic effect than either triamcinolone acetonide or flunisolide at doses appropriate for patients with mild-to-moderate persistent asthma.

Topics: Administration, Inhalation; Administration, Oral; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Area Under Curve; Asthma; Cosyntropin; Double-Blind Method; Female; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Prednisone; Triamcinolone Acetonide

Airway hyperresponsiveness, induced sputum eosinophils, and exhaled nitric oxide (NO) levels have all been proposed as non-invasive markers for monitoring airway inflammation in patients with asthma. The aim of this study was to compare the changes in each of these markers following treatment with inhaled glucocorticosteroids in a single study.. In a randomised, double blind, placebo controlled, parallel study 25 patients with mild asthma (19-34 years, forced expiratory volume in one second (FEV1) >75% predicted, concentration of histamine provoking a fall in FEV1 of 20% or more (PC20) <4 mg/ml) inhaled fluticasone propionate (500 microg twice daily) for four weeks. PC20 to histamine, sputum eosinophil numbers, and exhaled NO levels were determined at weeks 0, 2, and 4, and two weeks after completing treatment. Sputum was induced by inhalation of hypertonic (4.5%) saline and eosinophil counts were expressed as percentage non-squamous cells. Exhaled NO levels (ppb) were measured by chemiluminescence.. In the steroid treated group there was a significant increase in PC20, decrease in sputum eosinophils, and decrease in exhaled NO levels compared with baseline at weeks 2 and 4 of treatment. Subsequently, each of these variables showed significant worsening during the two week washout period compared with week 4. These changes were significantly different from those in the placebo group, except for the changes in sputum eosinophils and exhaled NO levels during the washout period. There were no significant correlations between the changes in the three markers in either group at any time.. Treatment of asthmatic subjects with inhaled steroids for four weeks leads to improvements in airway hyperresponsiveness to histamine, eosinophil counts in induced sputum, and exhaled nitric oxide levels. The results suggest that these markers may provide different information when monitoring anti-inflammatory treatment in asthma.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Biomarkers; Breath Tests; Bronchial Hyperreactivity; Bronchial Provocation Tests; Double-Blind Method; Eosinophils; Female; Fluticasone; Glucocorticoids; Histamine; Humans; Hypersensitivity, Immediate; Leukocyte Count; Male; Nitric Oxide; Sputum

Current treatment guidelines define inhaled corticosteroids such as fluticasone propionate (FP) as the cornerstone of anti-inflammatory therapy for asthma.. The objective was to evaluate the efficacy and safety of adding salmeterol therapy to patients who remain symptomatic while receiving FP as compared with increasing the dose of FP.. In a multicenter, double-blind study conducted over 24-weeks, 437 patients aged 12 years and older and receiving FP 88 microg twice daily for 2 to 4 weeks were randomly assigned to receive either salmeterol (42 microg twice daily) or FP 220 microg twice daily. The primary efficacy endpoint was morning peak expiratory flow. Secondary measures included FEV1, symptom scores, nighttime awakenings, and supplemental albuterol use. Safety was assessed by reported adverse events and asthma exacerbations.. The addition of salmeterol resulted in significantly greater improvements in lung function and symptom control as compared with increasing the dose of FP. Over weeks 1 to 24, morning peak expiratory flow was increased by 47 L/min from baseline with salmeterol treatment as compared with 24 L/min with FP 220 microg twice daily (P < .001) while the percent of symptom-free days increased from baseline by 26% of days as compared with 10% of days (P < .001). The adverse event profiles were similar between groups and fewer exacerbations were reported with salmeterol treatment.. The addition of salmeterol therapy to patients who remain symptomatic while using a low dose of FP was clinically and statistically superior to increasing the dose of FP.

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Respiratory Function Tests; Salmeterol Xinafoate

Plasma protein exudation into the airways is an important pathophysiological event in asthma. The effect of 12 wk of treatment with inhaled fluticasone propionate (FP; 250 microgram twice a day) or salbutamol (Sb; 400 microgram twice a day) on plasma protein leakage was compared in a double-blind, randomized parallel-group study of 30 patients with asthma. Primary outcomes were plasma protein leakage and size selectivity of the blood-airway lumen barrier, cell differentials in BAL fluid, and bronchial responsiveness to histamine (PC20histamine). Two independent procedures to account for the effect of variable dilution of BAL on the levels of albumin (Alb) and alpha2-macroglobulin (A2M) in BAL fluid consisted of correction based on urea levels and on the application of the relative coefficient of excretion [RCE = ([A2M] in BAL fluid/[A2M] in serum)/([Alb] in BAL fluid/[Alb] in serum)]. In the FP group a significant decrease was found in the A2M level and the RCE, and in the percentage of eosinophils in BAL fluid. The PC20histamine increased significantly (mean increase, 2.4 doubling doses), whereas PC20histamine decreased in the Sb group. Differences between groups were significant except for the decrease in eosinophils. We conclude that 12 wk of FP (250 microgram twice a day) decreased the permeability of the blood-airway lumen barrier, in particular for high molecular weight proteins.

Topics: Administration, Inhalation; Administration, Topical; Adult; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Blood Proteins; Blood-Air Barrier; Bronchodilator Agents; Capillary Permeability; Double-Blind Method; Exudates and Transudates; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged

The objective of this multicentre, randomised, double blind, parallel group study was to compare the efficacy and safety of the addition of salmeterol with that of doubling the dose of fluticasone propionate in asthmatic patients not controlled by a low or intermediate dose of inhaled corticosteroids.. After a four week run in period of treatment with fluticasone propionate (100 micrograms twice daily if pre-trial dose was 400-600 micrograms inhaled corticosteroids or 250 micrograms twice daily if pre-trial dose was 800-1200 micrograms inhaled corticosteroids), 274 patients were randomised to treatment for 12 weeks with either salmeterol 50 micrograms twice daily plus the run in dose of fluticasone propionate or twice the run in dose of fluticasone propionate (200 or 500 micrograms twice daily). Outcome measures were daily records of peak expiratory flow (PEF), symptom scores, and clinic lung function.. The improvements in both the morning and evening PEF were better in the salmeterol than in the fluticasone propionate group, the mean increase in morning PEF being 19 l/min higher (95% CI 11.0 to 26.1) and in evening PEF being 16 l/min (95% CI 18.4 to 24.0) higher in the salmeterol group. The increase in forced expiratory volume in one second (FEV1) was 0.09 1 greater in the salmeterol group than in the fluticasone propionate group after four weeks of treatment (95% CI 0.01 to 0.18), but not after 12 weeks. Both regimens showed an increase in symptom free days and a reduction in the need for rescue salbutamol both during the day and the night, but these improvements were greater in the salmeterol group. There were no significant differences between the groups in adverse effects or in the number of rescue course of oral corticosteroids.. In this group of patients still symptomatic despite 100 or 250 micrograms fluticasone propionate twice daily, the addition of salmetterol caused a greater improvement in lung function and symptom control than doubling the dose of fluticasone propionate.

Topics: Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Vital Capacity

Inhaled corticosteroids are recognised as the most effective agents in the treatment of asthma. However, concerns have been expressed about the effects of high doses of inhaled corticosteroids on safety in relation to bone resorption and formation. This study measures the effects of two inhaled corticosteroids on bone markers and bone mineral density (BMD) over one year.. A one year randomised, prospective, open parallel study comparing inhaled fluticasone propionate (FP), 500 micrograms twice daily in 30 patients, and budesonide (BUD), 800 micrograms twice daily in 29 patients, delivered by metered dose inhaler and large volume spacers was performed in adults with moderate to severe asthma. Biochemical markers of bone turnover (osteocalcin, procollagen type 1 C-terminal propeptide (PICP), immunoreactive free deoxypyridinoline (iFDpd), N-terminal crosslinked telopeptides of type I collagen (NTx)), BMD at the spine and femoral neck, and serum cortisol concentrations were measured at baseline and 12 months later.. There were no significant differences between the inhaled steroids on bone markers of bone resorption and formation or bone mineral density. Bone mineral density of the spine increased slightly in both groups over the 12 month period. Serum osteocalcin levels increased from baseline in both treatment groups (FP 16.9%, p = 0.02; BUD 14.3%, p = 0.04). PICP did not differ significantly from baseline. Both markers of bone resorption (iFDpd, NTx) varied considerably with no significant changes after one year. There was a significant correlation in percentage change from baseline between BMD of the spine and osteocalcin at 12 months (r = 0.4, p = 0.017). Mean serum cortisol levels remained within the normal range in both groups following treatment.. There was no evidence of a decrease in BMD during 12 months of treatment with high doses of either FP or BUD. The change in spine BMD correlated with the increase in osteocalcin. Studies extending over several years are needed to establish whether these findings persist.

Topics: Administration, Inhalation; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Biomarkers; Bone Density; Bone Development; Bone Resorption; Budesonide; Female; Femur Neck; Fluticasone; Humans; Hydrocortisone; Male; Middle Aged; Prospective Studies; Spine

The effectiveness of inhaled glucocorticoids in the treatment of asthma is well documented; however, times to onset and maximal treatment effects of these agents have been poorly described.. We sought to determine the time to onset of effect and the time to the best observed effect of inhaled fluticasone propionate (FP) in patients with asthma.. Data from 8 randomized, double-blind, placebo-controlled clinical trials of at least 8 weeks' duration were analyzed. Corticosteroid-naive patients (n = 1461) were treated with either FP (25 micrograms to 500 micrograms) or placebo twice daily. Efficacy evaluations included morning peak expiratory flow (PEF), asthma symptom scores, supplemental albuterol use, and FEV1.. Statistically significant improvements in PEF, asthma symptom scores, and supplemental albuterol use were observed beginning on day 1 of treatment in the FP group versus the placebo group (P <.001); significant increases in FEV1 were observed at the first measurement at week 1 (P <.001). The best observed effect occurred within 3 weeks of the start of FP treatment for PEF (+36 L/min) and FEV1 (+0.52 L) and within 2 weeks for reduction in supplemental albuterol use and asthma symptom scores. Patients with the most severe airflow obstruction had the greatest change in PEF (+56 L/min) and fastest time to 50% of best observed effect (3 days) compared with patients with mild or moderate airflow obstruction; however, time to best observed effect was similar in the 3 groups (20 to 27 days).. In patients with asthma, the onset of significant benefit of FP on PEF, symptoms, and rescue albuterol use occurred within 1 day of the start of therapy. FEV1 improved within 1 week of the start of therapy (the first measurement after randomization). There was no effect of sex, age, or dose of FP on the time to response. The best observed response in PEF varies with the degree of baseline airflow obstruction; however, the degree of airflow obstruction has no effect on the time to best observed response.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Circadian Rhythm; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Placebos; Time Factors

Inhaled corticosteroids are recommended for the treatment of persistent asthma. Comparative clinical studies evaluating 2 or more doses of these agents are few.. We sought to compare the efficacy and safety of 2 doses of fluticasone propionate (88 micrograms twice daily and 220 micrograms twice daily) with 2 doses of beclomethasone dipropionate (168 micrograms twice daily and 336 micrograms twice daily) in subjects with persistent asthma.. Three hundred ninety-nine subjects participated in this randomized, double-blind, parallel-group clinical trial. Eligible subjects were using daily inhaled corticosteroids and had an FEV1 of 45% to 80% of predicted value. Clinic visits, including spirometry, were conducted every 1 to 2 weeks. Subjects recorded symptoms, use of albuterol, and peak expiratory flows on daily diary cards.. Fluticasone propionate treatment resulted in significantly (P

Topics: Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Respiratory Function Tests; Severity of Illness Index; Tachycardia

As both rhinitis and asthma are allergic conditions, they frequently occur together. The objective of this study was to assess the diurnal adrenocortical activity in asthmatics receiving inhaled (inh) and intranasal (n) formulations of two different corticosteroids, fluticasone propionate (FP) and triamcinolone acetonide (TAA), both given at clinically recommended doses.. Twelve stable moderately severe asthmatic subjects of mean age 23.9 years and mean forced expiratory volume in one second (FEV1) 84% predicted were recruited into a randomised placebo (PL) controlled two-way crossover study comparing nPL + inhPL, nPL + inhFP (880 micrograms bid), and nFP (200 micrograms once daily) + inhFP (880 micrograms bid) with nPL + inhPL, nPL + inhTAA (800 micrograms bid) and nTAA (220 micrograms once daily) + inhTAA (800 micrograms bid), each given for five days with a 10 day washout period. Twenty four hour integrated and fractionated (overnight, 08.00 hours, daytime) serum cortisol levels and urinary cortisol/creatinine excretion were measured.. For 24 hour and fractionated serum cortisol levels and corrected urinary cortisol/creatinine excretion there were significant (p < 0.05) differences between all active treatments and placebo. For 24 hour integrated serum cortisol levels the ratio between inhaled TAA and FP was 2.3 fold (95% CI 1.2 to 4.3), and for 24 hour urinary cortisol/creatinine excretion the ratio was two-fold (95% CI 1.2 to 3.4). For 24 hour urinary cortisol excretion, with all active treatments, individual abnormal low values of < 40 nmol (< 14.4 micrograms) occurred in 17/24 with FP compared with 4/24 with TAA (p < 0.0005). The 24 hour serum cortisol profile was flattened by FP but not with TAA. The addition of nasal corticosteroid did not produce further significant suppression of mean cortisol values, although with intranasal FP there were three more abnormal values for 24 hour urinary cortisol excretion than with inhaled FP alone.. Both inhaled FP and TAA caused significant suppression of adrenocortical activity which was twice as great with FP, the latter being associated with significantly more individual abnormal values and loss of the normal diurnal circadian rhythm. Fractionated serum cortisol levels and urinary cortisol/creatinine excretion were as sensitive as the respective integrated 24 hour measurements. Although the addition of intranasal formulations did not produce further significant suppression of mean values, there were more individual abnormal cortisol values associated with the addition of intranasal FP.

Topics: Administration, Inhalation; Administration, Intranasal; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Cross-Over Studies; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Rhinitis; Single-Blind Method; Triamcinolone Acetonide

Although inhaled corticosteroids are widely used for the treatment of inflammation in asthma, prospective, long-term, placebo-controlled trials characterizing their systemic safety with chronic use are lacking.. This study was designed to prospectively evaluate the long-term safety of inhaled fluticasone propionate therapy.. Fluticasone propionate powder, 500 microgram, or placebo was administered twice daily by means of the Diskhaler for 104 weeks to 64 adults with mild persistent asthma in a randomized, double-blind, parallel-group study. Primary safety variables were measured at baseline and every 6 months thereafter. Although evaluation of efficacy was not an objective of this study, pulmonary function testing was performed at monthly intervals.. Two years of treatment with fluticasone propionate had no significant effects on the skeletal system. No clinically significant changes were observed in ophthalmic parameters (glaucoma and posterior subcapsular cataracts). Mean change from baseline in lumbar spine (L1 to L4 ) bone density at week 104 was not significantly different between fluticasone propionate (-0.006 +/- 0.008 g/cm2) and placebo (-0.007 +/- 0.010 g/cm2). Markers of bone formation (serum osteocalcin) and resorption (urinary N-telopeptide) did not differ significantly between treatment groups. The effects of fluticasone propionate treatment on the hypothalamic-pituitary-adrenal axis were minimal, with no alterations in morning plasma cortisol concentrations and minor but statistically significant decreases in poststimulation mean peak plasma cortisol concentrations (P =.021) and 8-hour plasma cortisol area under the curve values (P =.020) at week 104. Drug-related adverse events were primarily topical effects of inhaled corticosteroids. Pulmonary function improved significantly during 2 years of fluticasone propionate treatment.. Fluticasone propionate powder, 500 microgram twice daily for up to 2 years, was efficacious and well tolerated, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis, bone density, or ophthalmic parameters in adults with mild asthma.

Topics: Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Bone Density; Bone Resorption; Double-Blind Method; Female; Fluticasone; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Osteogenesis; Patient Compliance; Pituitary-Adrenal System; Powders

While inhaled steroids (IS) are increasingly recognized as having a more rapid onset of action than was once thought, little is known about the early changes in objective measures of respiratory function that follow the inhalation of repeated doses. These early effects were examined in a randomized, double-blind, placebo-controlled, crossover study of 20 children aged 10-16 years with stable mild asthma. Beclomethasone dipropionate (BDP) 2,000 mcg, fluticasone propionate (FP) 400 mcg, and placebo were given twice daily for three doses. Airway hyperreactivity (AHR) to methacholine (PC20), pulmonary function tests (PFT: FVC, FEV1, FEF25-75%), and the rate of recovery from methacholine-induced bronchospasm following administration of salbutamol were determined at 8 h (after 1 dose) and at 32 h (after three doses). At 8 h, minor improvements in AHR were demonstrated, averaging 0.32 doubling doses in PC20. At 32 h, significant improvements in AHR and PFTs were present, averaging 0.92 doubling doses in PC20, 3.96% of predicted values in FEV1, and 7.74% of predicted values in FEF25-75%. No significant changes occurred in FVC. There were no significant differences between the effects of BDP and FP. Inhaled steroids were associated with a slower response to salbutamol following methacholine challenge testing at 32 h. We conclude that IS, given in repeated high doses, result in significant improvements within 32 h in both AHR and PFTs, along with changes in response to beta2 agonists. These effects are likely to be the result of the topical activity of IS.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Child; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Respiratory Function Tests; Respiratory Mechanics; Treatment Outcome

Some patients with severe asthma are difficult to control and suffer from frequent exacerbations, whereas others remain stable with anti-inflammatory therapy. To investigate mechanisms of exacerbations, we compared 13 patients 20 to 51 yr of age (11 female, two male) with difficult-to-control asthma (two or more exacerbations during the previous year) and 15 patients 20 to 47 yr of age (13 female, two male) with severe but stable asthma (no exacerbations) after matching for sex, age, atopy, lung function, airway responsiveness, and medication. Exacerbations were induced by double-blind, controlled tapering of inhaled corticosteroids (fluticasone propionate) at weekly intervals. FEV1, airway responsiveness for methacholine (PC20MCh) and hypertonic saline (HYP slope), eosinophils and soluble markers (ECP, albumin, IL-6, IL-8) in induced sputum were assessed at baseline and during exacerbation (peak flow < 60% of personal best), or after 5 wk if no exacerbation occurred. Steroid tapering caused a decrease (mean +/- SEM) in FEV1 (12.1 +/- 3.1% pred; p = 0.045), PC20MCh (2.1 +/- 0.4 doubling dose; p = 0.004) and HYP slope (1.7 +/- 0.3 doubling dose; p = 0.001), and an increase in sputum eosinophils (10 +/- 3%; p = 0.008) and soluble markers for the two groups combined, without significant differences between the groups. Patients with difficult-to-control asthma had more exacerbations than did the stable asthmatics during both steroid tapering (7 versus 2; p = 0.022) and corticosteroid treatment (6 versus 0; p = 0.003). Exacerbations during steroid treatment in the patients with difficult-to-control asthma were associated with a decrease in FEV1 and PC20MCh, but not in HYP slope or increase in sputum eosinophils. We conclude that tapering of inhaled corticosteroids induces a rapid, reversible flare-up of eosinophilic airway inflammation. Patients with difficult-to-control asthma may develop exacerbations despite treatment with inhaled corticosteroids, which appear to have an eosinophil-independent mechanism. This implies that assessment of the nature of exacerbations may contribute to improved treatment for these patients.

Topics: Administration, Inhalation; Adult; Airway Resistance; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchial Provocation Tests; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Recurrence; Sputum; Substance Withdrawal Syndrome

The response in asthmatic young children to inhaled steroids within the usual pediatric dose range is unknown. We therefore evaluated the dose-related response in young children with moderate asthma to inhaled fluticasone propionate (FP) (delivered via the Babyhaler spacer device) within the pediatric dose range. A total of 237 children (mean age 28 mo, range 12 to 47) with moderate asthmatic symptoms were studied in this multicenter, randomized, double-blind, parallel group, placebo-controlled study of 12 wk treatment following a 4-wk run-in period. The median use of rescue medication was 1 dose in 2 d during the run-in period. FP 50 micrograms twice daily (FP100) and 100 micrograms twice daily (FP200) was compared with placebo inhaled from a pressurized metered-dose inhaler (pMDI) and the Babyhaler spacer device. With FP200 there was a statistically significant improvement from baseline, as compared with the placebo group, in 8 of 10 diary card parameters, including the three symptom domains of wheeze, cough, and breathlessness, and use of rescue medication. FP100 produced a significant reduction in 5 of these 10 parameters, whereas no significant differences were found between the FP200 and FP100. The numbers of patients with at least one exacerbation during treatment with placebo, FP100, and FP200 were 37%, 26%, and 20%, respectively. This difference between placebo and FP200, as well as the dose-related order was significant (p < 0.05). Both FP doses were as well tolerated as placebo over the 12 wk treatment with a similar incidence of adverse effects. Asthmatic symptoms in 1- to 3-yr-old children responded in a significant and dose-related manner to treatment with FP within a pediatric dose range.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Infant; Male

We assessed the systemic effects of budesonide (BUD) and fluticasone propionate (FP) in 23 patients with asthma, using a double-blind, placebo-controlled, double-dummy, and cross-over design. The following five treatments were given in a randomized order for 1 wk with a washout period in between of 2 wk: (1) placebo; (2) FP, 200 micrograms twice a day, inhaled from a Diskhaler; (3) FP, 1,000 micrograms twice a day, inhaled from a Diskhaler; (4) BUD, 200 micrograms twice a day, inhaled from a Turbuhaler; and (5) BUD, 800 micrograms twice a day, inhaled from a Turbuhaler. The primary variable was the area under the curve of serum cortisol versus time (AUC0-20), derived from serum samples taken every 2 h over a 20-h period following the last evening dose at 10:00 P.M. The lower doses of BUD and FLU did not cause any adrenal suppression. Compared with placebo, however, FP (1, 000 micrograms, twice daily and BUD (800 micrograms, twice daily) decreased the AUC0-20 by 34 and 16%, respectively. Fluticasone (1,000 micrograms, twice daily) was more suppressive than BUD (800 micrograms, twice daily) (p = 0.0006). The FEV1, measured the morning after the last inhalation, was significantly higher after the active treatments, compared with placebo (p < 0.02), but did not differ between all active treatments. We conclude that high doses of BUD and FP (in particular the latter), inhaled via their respective dry powder inhalers for 1 wk, result in a measurable systemic activity in patients with asthma.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate

Fluticasone propionate (FP) is generally considered to have twice the efficacy of beclomethasone dipropionate (BDP) on a weight-to-weight basis for the control of asthma, and may have lesser effects on adrenal function. However, the effects of FP and BDP on skin integrity and bone metabolism markers require further examination. Sixty-nine asthmatic subjects were enrolled in a double-blind crossover study in which, after a baseline period, they received BDP or FP (at half the dose of BDP) for two 4-month periods each. A questionnaire on skin bruising, a skin examination, tests of adrenal function and of markers of bone metabolism were performed after 2 months of each period. The number of asthma exacerbations was not significantly different for the two treatment periods (eight for BDP and nine for FP), nor were various indices of asthma control. Whereas the frequency of bruising reported by the questionnaire was not different, there were more bruises on examination for BDP (1.6+/-2.5) than for FP (1.2+/-2.3) (p=0.04). Although baseline serum cortisol was not significantly different for the two drugs, the increase in cortisol after cortrosyn was lower for BDP (357+/-158 micromol x dL(-1)) than for FP (422+/-144 micromol x dL(-1)) (p<0.01). Serum osteocalcin levels were significantly lower in subject on BDP (2.8+/-1.7 microg x mL(-1)) than on FP (3.5+/-1.9 ng x mL(-1)) (p=0.003). Other markers of bone metabolism were not significantly altered. The three major side-effects were loosely, but significantly correlated with the periods on BDP and FP. However, skin bruises, increase in cortisol after Cortrosyn and osteocalcin were not significantly correlated for the period on either BDP or FP. In conclusion, whereas fluticasone propionate used at half the dose of beclomethasone dipropionate has a comparable effect on the control of asthma, fluticasone propionate demonstrated fewer side-effects in terms of skin bruising, adrenal suppression and bone metabolism.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Contusions; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Middle Aged; Osteocalcin; Prospective Studies; Skin Diseases

Asthma is a chronic inflammatory disorder of the airways characterized by variable airflow limitation and airway hyperresponsiveness. The type of inflammatory response in asthma is compatible with a major contribution of professional antigen-presenting cells. The airways in chronic obstructive pulmonary disease (COPD) are also markedly inflamed; however, the predominant types of inflammatory cells and the main anatomical site of the lesion appear to differ from those in asthma. COPD is characterized by reduced maximum expiratory flow and slow forced emptying of the lungs. Steroids are the most prominent medication used in the treatment of asthma and COPD; however, the beneficial effect of steroid treatment in COPD is subject of debate. We investigated the efficacy of fluticasone propionate (FP) treatment in atopic asthmatics and in COPD patients with bronchial hyperreactivity who smoke. The effect of the treatment on bronchial hyperreactivity and indices of the methacholine dose-response curve were analysed, as well as indices of inflammation of the airway mucosa with special emphasis on the antigen presenting dendritic cell. Treatment of allergic asthmatic patients resulted in improvement of lung function (FEV1), a decrease in bronchial hyperresponsiveness and a decrease of maximal airway narrowing. During the FP-treatment of COPD patients, FEV1 remained stable, while FEV1 deteriorated significantly in the placebo group. Therefore, steroid treatment may have a beneficial effect in COPD patients with bronchial hyperresponsiveness (BHR). Since immunohistochemical analysis of bronchial biopsy specimens from asthma and COPD patients show disease-specific aspects of inflammation, the anti-inflammatory effect of FP is obtained through modulation of different cell populations in asthma and COPD.

Topics: Androstadienes; Animals; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Dendritic Cells; Dose-Response Relationship, Drug; Fluticasone; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Methacholine Chloride

Cross-sectional studies have suggested that asthmatic patients receiving high dose inhaled corticosteroids and intermittent courses of oral corticosteroids have reduced bone mass. This prospective 2-yr study was undertaken to evaluate changes in bone density of patients receiving high doses of inhaled corticosteroids. Patients (n = 33) (males aged 18-50 yrs, females aged 18-40 yrs) on inhaled corticosteroids 1,000-2,000 microg x day(-1), were randomized in a double-blind fashion to either fluticasone propionate (FP) 1,000 microg x day(-1) or beclomethasone dipropionate (BDP) 2,000 microg x day(-1). In parallel, three open control groups of the same age range were studied: asthmatics (n = 8) receiving low dose inhaled corticosteroids (< or =400 microg x day(-1)) (group A); chronic, severe asthmatics (n = 8) receiving oral corticosteroids (> or =10 mg x day(-1) (group B); and healthy untreated volunteers (n = 7) (group C). Bone densitometry scans (quantitative computed tomography (QCT) of spine; dual X-ray absorptiometry of spine, femoral neck, and single photon absorptiometry of forearm) were performed at baseline and after 6, 12 and 24 months of treatment. Biochemical bone marker measurements (serum osteocalcin, bone alkaline phosphatase, pro-collagen type 1 carboxy terminal propeptide, deoxypyridinoline and C-telopeptide of type 1 collagen) were collected every 3 months. Fifteen FP (mean age 36 yrs, six male) and 9 BDP patients (mean age 33 yrs, five male); completed the study. At 0 months, mean bone mineral density (BMD) was lower in patients receiving inhaled corticosteroids (both low dose and high dose) than in normal volunteers. In the FP-treated group, mean vertebral trabecular BMD quantitative computed tomography remained stable with no evidence of decline, whereas there was some decline in the BDP-treated group. The treatment difference between FP and BDP was statistically significant in favour of FP for quantitative computed tomography measurements after 12 months (p = 0.006) and 24 months (p = 0.004). This study suggests that over 24 months, changes in bone density are minimal in patients on high-dose inhaled corticosteroids.

Topics: Absorptiometry, Photon; Administration, Inhalation; Adolescent; Adult; Alkaline Phosphatase; Androstadienes; Asthma; Beclomethasone; Bone and Bones; Bone Density; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Osteocalcin; Peptide Fragments; Procollagen; Tomography, X-Ray Computed

Bronchial asthma is now agreed as being a chronic inflammatory disease of the airways. Inhaled steroids are widely accepted as a preventive medication in asthmatic patients of all ages and severity. However, the optimal use of inhaled steroids and the important issue of safety and efficacy still remain of concern, particularly in children. Recently, fluticasone propionate (FP) has been developed for use as an inhaled preparation for the treatment of asthma. Because of its high topical potency and increased lipophilicity, it is claimed that FP has an improved risk/benefit compared with other inhaled steroids. In order to evaluate the use of FP in children, we have studied the efficacy of high dose FP (500 microg/day) in asthmatic children. Thirteen children (9 boys and 4 girls), aged 7-17 years (10.8 +/- 2.6), were instructed to use a pressurized metered-dose inhaler connected to a Volumetric spacer. The standard methacholine bronchial challenge test was used as a principal outcome parameter. The PD20, a cumulative dose of methacholine inducing a 20% decrease in FEV1, was measured pre- and post-treatment with inhaled FP. After 4 weeks of FP, PD20 significantly increased from 21.6 +/- 14.3 inhalation unit to 106.6 +/- 78.5 inhalation unit (4.9 fold, p = 0.004) reflecting the improvement of airway reactivity. All subjects improved clinically. These results demonstrate that the anti-inflammatory action of FP 500 microg a day for four weeks can markedly reduce bronchial hyperresponsiveness, the basic physiologic abnormality in bronchial asthma.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Child; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Treatment Outcome

To compare the efficacies of medium-dose fluticasone propionate (FP), medium-dose triamcinolone acetonide (TAA), and combined low-dose FP plus salmeterol (SL).. Randomized, double-blind, triple-dummy, multicenter, 12-week clinical trial.. Allergy/respiratory care clinics.. Six hundred eighty patients with asthma previously uncontrolled with low-dose inhaled corticosteroids.. FP, 220 microg bid; TAA, 600 microg bid; or FP, 88 microg plus SL, 42 microg bid.. Outcome measures included FEV1, peak expiratory flow (PEF), supplemental albuterol use, nighttime awakenings, asthma symptoms, and physician global assessment. Compared with TAA, 600 microg bid, treatment with FP 220, microg bid, significantly increased FEV1, morning and evening PEF, and percent symptom-free days, and significantly reduced rescue albuterol use, number of nighttime awakenings, and overall asthma symptom scores (p < or = 0.035). Improvements with low-dose FP, 88 microg, plus SL, 42 microg bid, were significantly (p < or = 0.004) greater than TAA, 600 microg bid, in all the aforementioned efficacy measures as well as percent of rescue-free days. Combined low-dose FP, 88 microg, plus SL, 42 microg bid, also significantly increased FEV1 and percent of rescue-free days, and significantly reduced albuterol use compared with medium-dose FP, 220 microg bid (p < or = 0.018). At endpoint, both FP, 220 microg bid, and FP, 88 microg, plus SL, 42 microg bid, significantly increased FEV1 by 0.48 L and 0.58 L, respectively, compared with 0.34 L with TAA, 600 microg bid.. In patients who are symptomatic while taking low-dose inhaled corticosteroids, medium-dose FP (440 microg/d) and combination treatment with low-dose FP (176 microg/d) plus SL (84 microg/d) are both more effective than medium-dose TAA (1200 microg/d) in improving pulmonary function and asthma symptom control.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Sleep; Triamcinolone Acetonide

Recent studies suggest that inhaled corticosteroids may differ significantly in their systemic effects.. To compare the systemic effects, as measured by plasma cortisol suppression, of inhaled beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, and triamcinolone acetonide at doses of approximately 1000 microg twice daily.. Sixty healthy adult male volunteers participated in this randomized, open-label, parallel-design study. Twenty-four-hour plasma cortisol determinations (cortisol-AUC24) were measured after a single dose of placebo medication and after a single dose and 7 consecutive doses of active medication.. After a single dose, all inhaled corticosteroid preparations caused statistically significant mean reductions in cortisol-AUC24 compared with placebo as follows: flunisolide, 7% (P= .02); budesonide, 16% (P= .001); beclomethasone, 18% (P= .003); triamcinolone, 19% (P=.001); and fluticasone, 35% (P<.001). After multiple doses, flunisolide was not significantly different from placebo (5%; P = .24), while budesonide (18%; P = .002), triamcinolone (25%; P<.001), beclomethasone (28%; P<.001), and fluticasone (79%; P<.001) all resulted in statistically significant suppression of cortisol-AUC24. After both single and multiple doses, beclomethasone, budesonide, flunisolide, and triamcinolone were not statistically different from each other, while fluticasone was significantly (P<.001) more suppressive than the other 4 medications.. These results indicate that there are differences in the systemic effects of inhaled corticosteroids when used in high doses and emphasize the importance of using the minimum dose of inhaled corticosteroids required to maintain control of asthma symptoms.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Hydrocortisone; Male; Reference Values; Triamcinolone Acetonide; Volunteers

This study was designed to assess the relationship between the degree of airflow obstruction and the suppression of the hypothalamic-pituitary-adrenal axis after inhalation of fluticasone propionate (FP) in asthmatic patients with varying degrees of airway obstruction.. The nocturnal cortisol production (from 10:00 PM to 6:00 AM), defined as the integrated area under the curve of nocturnal plasma cortisol, was measured following inhalation of a placebo or a single dose of 500 microg FP at 8:00 PM in 28 patients with mild to moderate asthma, in a single, blind, 2-night study.. The mean morning rise of cortisol decreased significantly following a single dose of inhaled FP. When the total nocturnal cortisol production after the second night (when the FP was inhaled) was compared to that after the first night (when the placebo was administered), it was found to have decreased by 29.4%. There was a statistically significant correlation between the FEV(1) and the fall in cortisol production just before the inhalation of FP (p < 0. 001). There was no correlation between baseline cortisol production and the fall in cortisol production.. Our findings suggest that the degree of airway obstruction affects the systemic bioavailability of FP. FP is likely to induce a more severe decrease in nocturnal cortisol secretion in less obstructed patients. In order to reduce the risk for systemic side effects, the patient's degree of airway obstruction should be considered when planning inhaled FP treatment.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Biological Availability; Circadian Rhythm; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Powders; Single-Blind Method

Inhaled corticosteroids such as fluticasone propionate (FP) have dose-related systemic effects, including adrenal suppression. We have therefore investigated the effect of adding a large volume spacer on the systemic bioactivity of FP given via a pressurized metered-dose inhaler (pMDI).. Fourteen healthy volunteers (mean age, 29.9 years old) were studied using an open, randomized, placebo-controlled, three-way crossover design. Single doses of the following were given at 5:00 PM in a randomized sequence: (1) eight puffs of FP by pMDI, 1.76 mg (250 microg ex-valve, 220 microg ex-actuator); (2) eight puffs of FP by pMDI, 250 microg, with 750-mL spacer (Volumatic; Allen & Hanburys; Uxbridge, UK); and (3) eight puffs of placebo by pMDI. Measurements were made after each dose, including overnight and early morning urinary cortisol/creatinine ratios and 8:00 AM serum cortisol.. Significant (p < 0.05) suppression of all three end points occurred with each active treatment compared to treatment with placebo. Furthermore, significant (p < 0.05) additional suppression occurred when comparing FP by pMDI alone to FP by pMDI with spacer. Geometric mean fold differences (95% confidence interval for fold difference) between FP by pMDI alone and FP by pMDI with spacer were 1.94-fold (1.00-3.78) for overnight urinary cortisol/creatinine ratio and 1.98-fold (1.26-3.10) for 8:00 AM serum cortisol. This was mirrored by a twofold rise in the number of values for uncorrected overnight urinary cortisol < 10 nmol/10 h: placebo treatment (none of 14 subjects); FP by pMDI (6 of 14 subjects; 43%); and FP by pMDI with spacer (12 of 14 subjects; 86%).. The use of a large volume spacer with FP by pMDI results in a twofold increase in the systemic bioavailability as assessed by sensitive measures of adrenal suppression. This, in turn, reflects a twofold improvement in respirable dose delivery with the spacer device.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Biological Availability; Circadian Rhythm; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Equipment Design; Fluticasone; Humans; Hydrocortisone; Nebulizers and Vaporizers

Inhaled corticosteroids have become the mainstay of asthma therapy. Few studies however, have compared inhaled steroids in children. We compared the efficacy of inhaled fluticasone propionate (FP), 880 microg/day (2 puffs of 220 microg/puff, BID) with inhaled flunisolide (FLU), 1500 microg/day (3 puffs of 250 microg/puff, BID).. Thirty children with moderate to severe asthma, mean age 12.7 years (range 10 to 17 years), mean duration of asthma 8.4 years, initially received flunisolide 1500 microg/day for 1 year, and then were switched to fluticasone propionate 880 microg/day and followed for an additional year. Pulmonary function tests (PFTs) were monitored and analyzed before and after the switch for the duration of study. Mean percent predicted for age values for FVC, FEV1, FEF25-75%, and FEFR were compared at 1 month, 2 to 6-month intervals, and 7 to 12-month intervals and during the same season of the year. Pulmonary function tests within 3 weeks of an exacerbation were not included in the study. The number of asthma exacerbations, emergency room visits, hospital admissions, and number of school days lost were also compared.. There was significant improvement in mean asthma exacerbations/patient/year (1.7 +/- 1.66 SD) versus (4 +/- 2.6) (P < .0002); mean emergency room visits/patient/year (0.23 +/- 0.62) versus (1.2 +/- 1.74) (P = .004); mean hospital admissions for asthma/patient/year (0.2 +/- 0.61) versus (1.13 +/- 1.45) (P < .0002); and number of school days lost/patient/year (1.4 +/- 2.38) versus (7.93 +/- 6.7) (P < .0002) while patients were receiving fluticasone propionate as compared with flunisolide. Also, the mean percent values predicted for age in all time-periods (at 1 month, 2 to 6 months, and 7 to 12 months) revealed significant improvement in FEV1 and FEF25-75% (P < .05 for both parameters). As PFT can be affected by seasonal changes, PFT parameters were compared during the same season of the year and significant improvement in FVC and FEV1 was observed in all seasons while patients were receiving fluticasone propionate (FP) compared with flunisolide (FLU) (P < .05 for all parameters). Significant improvement in PEFR and FEF25-75% was observed only in spring and summer season.. Fluticasone propionate 880 microg/day improved lung function and quality of life in adolescents with moderate-to-severe asthma when compared with flunisolide 1500 microg/day.

Topics: Absenteeism; Administration, Inhalation; Adolescent; Albuterol; Androstadienes; Asthma; Child; Cross-Over Studies; Drug Therapy, Combination; Emergencies; Female; Fluocinolone Acetonide; Fluticasone; Follow-Up Studies; Hospitalization; Humans; Male; Nebulizers and Vaporizers; Pulmonary Ventilation; Salmeterol Xinafoate; Seasons; Spirometry; Theophylline; Treatment Outcome

The addition of long-acting beta(2) agonists to inhaled corticosteroid (ICS) therapy in symptomatic patients with asthma improves clinical status more than increasing the dose of ICS. It has been suggested that these benefits could be at the cost of an increase in airway inflammation, but few histopathological studies have been performed in the relevant group. In a double-blind, parallel-group, placebo-controlled study, we randomly assigned 50 symptomatic patients with asthma who were receiving ICS (range, 100 -500 microgram/d) to 12 wk of supplementary treatment with salmeterol (50 microgram twice daily) or fluticasone (100 microgram twice daily) or placebo. Bronchial biopsies and BAL were obtained from 45 patients before and after treatment and analyzed. After treatment with salmeterol there was no deterioration of airway inflammation as assessed by mast cells, lymphocytes, or macrophages in BAL or biopsies, but rather a significant fall in EG1-positive eosinophils in the lamina propria (from a median 18.3 to 7.6 cells/mm, p = 0.01), which was not seen after treatment with fluticasone. The only cellular effect of added fluticasone was a decrease in BAL lymphocyte activation. There was a concurrent improvement in clinical status, more marked with salmeterol than with increased ICS. Thus, adding salmeterol to ICS is not associated with increased "allergic" airway inflammation, but conversely with a complementary antieosinophil effect.

Topics: Adrenergic beta-Agonists; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Biopsy, Needle; Bronchi; Bronchoalveolar Lavage Fluid; Double-Blind Method; Eosinophils; Fluticasone; Forced Expiratory Volume; Humans; Inflammation; Lymphocytes; Macrophages; Mast Cells; Peak Expiratory Flow Rate; Salmeterol Xinafoate

Inhaled steroids, delivered by metered dose aerosol and dry powder inhalers, have proved effective in reducing the need for oral steroids in patients with oral steroid-dependant asthma. This randomized, double-blind study, compared the efficacy and tolerability of nebulized fluticasone propionate (FP Nebules), 2 mg b.d. (FP 4 mg) and 0.5 mg b.d. (FP 1 mg) with placebo, on the reduction of oral steroid requirement in 301 adult patients with oral steroid-dependent asthma. Primary efficacy was assessed by the reduction in daily oral steroid dose. Secondary efficacy parameters included daily diary card peak expiratory flow (PEF), day and night-time symptoms and clinic lung function measurements. Safety was assessed by adverse event monitoring and serum cortisol levels. After 12 weeks of treatment the adjusted mean +/- SEM reduction in oral prednisolone was significantly greater in the FP 4 mg group (4.44 +/- 0.98 mg day-1) compared with FP 1 mg (2.16 +/- 1.00 mg day-1, P = 0.039) and placebo (1.20 +/- 1.02 mg day-1, P = 0.004). A higher percentage of patients discontinued the use of oral steroids with FP 4 mg (37%) compared with FP 1 mg (26%, P = 0.038) and placebo (18%, P < 0.001). Following treatment, the adjusted mean morning PEF showed a trend in favour of FP 4 mg (280 +/- 41 min-1) compared with placebo (270 +/- 51 min-1, P = 0.053) and the evening PEF was significantly higher with FP 4 mg (305 +/- 41 min-1) compared with FP 1 mg (292 +/- 41 min-1, P = 0.010). FP 4 mg resulted in a significantly higher percentage of days when the patients were free from daytime (P = 0.036) and night-time (P = 0.021) wheeze, compared with placebo. Significantly fewer patients withdrew from the FP 4 mg group compared with the other two groups (vs. FP 1 mg, P = 0.003; vs. placebo, P = 0.032). All three treatments were well tolerated and the incidence of adverse events was similar between the groups. FP Nebules at a daily dose of between 1 and 4 mg are a safe and effective means of reducing the oral steroid requirement of patients with chronic oral steroid dependent asthma.

Topics: Adolescent; Adult; Aged; Androstadienes; Animals; Anti-Inflammatory Agents; Asthma; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Prednisolone; Time Factors

To determine the systemic dose-response relationships with oral prednisolone and inhaled fluticasone propionate administered in a putative 11:1 mg equivalent basis, in terms of effects on adrenal, bone and haematological markers.. Twelve asthmatic patients mean (s.e.) age, 28.8 [3.3] years, FEV1 94.7 [3.6]% predicted, FEF(25-75) 65.5 [6.1]% predicted were studied in a double-blind, double dummy randomised crossover design comparing placebo, inhaled fluticasone propionate via volumatic spacer given twice a day (ex actuator dose 0.44 mg day-1, 0.88 mg day-1, 1.76 mg day-1 ) and oral prednisolone given once daily (5 mg day-1, 10 mg day-1, 20 mg day-1 ). All treatments were for 4 days at each dose level with a 7-day washout at crossover. Measurements were made at 08.00 h after the last dose of each dose level for plasma cortisol, serum osteocalcin and blood eosinophil count.. There were significant dose-related effects for suppression of all three endpoints with both prednisolone and fluticasone propionate. Parallel slope analysis revealed a calculated dose ratio for relative potency of 8. 5:1 mg (95% CI 5.7-11.2) comparing Pred with FP for morning cortisol. The magnitude of suppression with FP was less for osteocalcin and eosinophils than for cortisol.. Systemic tissues exhibit different dose-response relationships for the effects of inhaled and oral corticosteroids with suppression of cortisol being greater than osteocalcin or eosinophils. For cortisol suppression we observed an 8.5:1 mg relative potency ratio comparing prednisolone with fluticasone propionate. Patients taking high dose inhaled fluticasone propionate should therefore be screened for evidence of impaired adrenal reserve.

Topics: Administration, Inhalation; Administration, Oral; Adrenal Glands; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Biomarkers; Bone and Bones; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophils; Female; Fluticasone; Humans; Hydrocortisone; Male; Osteocalcin; Prednisolone; Time Factors

This multicentre double-blind, double-dummy study compared the safety and efficacy of a new combination Diskus inhaler containing both salmeterol 50 microg and fluticasone propionate 500 microg (Seretide, GlaxoWellcome, France) with the same doses of the two drugs delivered via separate Diskus inhalers and with the same dose of fluticasone propionate alone. Patients were eligible for study entry if they had received an inhaled corticosteroid continuously for 12 weeks prior to run-in, and had received treatment with beclomethasone dipropionate or budesonide 1500-2000 microg day(-1) or fluticasone propionate 750-1000 microg day(-1) for at least 4 weeks prior to run-in. In total, 503 patients receiving inhaled corticosteroids were randomized to 28 weeks' treatment with either salmeterol/fluticasone propionate (50/500 microg) via a single Diskus inhaler (combination) and placebo, or salmeterol 50 microg and fluticasone propionate 500 microg administered via separate Diskus inhalers (concurrent), or fluticasone propionate 500 microg and placebo. All treatments were administered twice daily, mean morning peak expiratory flow rate (PEFR) and asthma symptoms were measured for the first 12 weeks and safety data were collected throughout the 28-week study. Over weeks 1 to 12, improvement in adjusted mean morning PEFR was 35 and 33 l min(-1), respectively, in the combination and concurrent therapy treatment groups (12 and 10% increase from baseline, respectively). The mean difference between treatments was -3 l min(-1) (90% confidence interval -10.4 l min(-1)) which was within the criteria for clinical equivalence. However, the combination therapy was statistically significantly superior to fluticasone propionate alone for mean morning PEFR (P<0.001) and other measures of lung function, whilst clinical equivalence of the combination and concurrent therapies was observed. All three treatments were well tolerated. In addition, there were no differences between the three treatments in either the c.hange in serum cortisol or urinary cortisol concentrations, which, for each treatment group, were no significantly different from baseline at the end of the treatment period. Thus, the combination of salmeterol and fluticasone propionate in a single inhaler is as well tolerated and effective in achieving asthma control in steroid-dependent patients as the separate administration of the two drugs, and both combination and concurrent therapy are superior to administration of th

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Salmeterol Xinafoate

The aim of this study was to determine the cost effectiveness of 2 inhaled corticosteroids, fluticasone propionate and flunisolide, in the management of asthma from a third-party payer perspective in Germany (German Sickness Fund).. Direct treatment costs were retrospectively applied to 2 prospective randomised parallel group clinical trials conducted in Germany comparing fluticasone propionate and flunisolide: one 6-week open-label study (n = 332) and one 8-week double-blind study (n = 308) in corticosteroid-naive patients with asthma of moderate severity aged between 18 and 70 years. All costs were adjusted to 1997 Deutschmarks. Efficacy parameters included changes in morning and evening peak expiratory flow rate (PEFR) measurements, the number of successfully treated patients (defined as those with a PEFR improvement of > or = 10%) and proportion of symptom-free days.. The fluticasone propionate groups had higher respective proportions of successfully treated patients and symptom-free days than the flunisolide groups in both the open-label (56.8 vs 39.6% and 36.4 vs 28.5%) and double-blind (55.3 vs 44.5% and 35.1 vs 31.1%) studies. Improvements in both morning and evening PEFR measurements were also significantly (p < 0.01) greater with fluticasone propionate than with flunisolide. Although average daily treatment costs were slightly higher in the fluticasone propionate groups than in the flunisolide groups, all cost-effectiveness ratios (daily cost per successfully treated patient and daily cost per symptom-free day) favoured fluticasone propionate. Sensitivity analysis showed that these results were robust over a wide range of assumptions.. In these patients, management with fluticasone propionate was more cost effective than with flunisolide in the German healthcare setting.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Cost-Benefit Analysis; Double-Blind Method; Female; Fluocinolone Acetonide; Fluticasone; Germany; Glucocorticoids; Humans; Male; Middle Aged; Prospective Studies

Topics: Adolescent; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Cost-Benefit Analysis; Double-Blind Method; Drug Combinations; Female; Fluticasone; Humans; Male; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Salmeterol Xinafoate

Inhaled steroids are frequently used in childhood asthma, but concerns based on limited objective evidence remain, regarding long-term side-effects. In this study the systemic effects of standard doses of inhaled steroids in childhood asthma were assessed, comparing beclomethasone dipropionate (BDP) with fluticasone propionate (FP). The study was prospective, randomized and double-blind. Twenty-three steroid-naive children with moderately severe asthma, aged 5-10 yrs, were allocated either BDP (400 microg x day(-1) or FP (200 microg x day(-1)) using a metered-dose inhaler with a spacer. Asthma control was assessed at regular intervals over 20 months. Fasting morning blood and overnight urine samples were collected for estimation of serum cortisol, serum 1-carboxyterminal telopeptide (ICTP), serum osteocalcin and urine deoxypyridinoline (DPD). Bone mineral density (BMD) was measured at each visit. None of the markers of bone turnover showed any change during the study period. BMD increased at normal rates with age. Serum cortisol significantly decreased on BDP, but not on FP. A significant difference in growth rates was found between the groups, with a slower rate of growth towards the end of the observation period in the BDP group. In conclusion when taken in a relatively modest dose over a period of time, beclomethasone dipropionate had significant effects on the hypothalamic-pituitary-adrenal axis and statural growth in childhood asthma. These systemic effects were not seen with an equipotent dose of fluticasone propionate.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bone Remodeling; Child; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Growth; Humans; Male; Prospective Studies

The aim of this study was to evaluate the steady-state effects of once-daily inhaled fluticasone propionate (FP) and budesonide (BUD) on adrenocortical activity in asthmatic patients.. Ten asthmatic patients with a mean age of 31.2 years, a mean forced expiratory volume in 1 s (FEV1) of 91% predicted and a forced mid-expiratory flow (FEF25-75) of 62.3% predicted were studied in a single-blind randomised crossover design comparing placebo (PL), FP (375 microg per day and 750 microg per day) and BUD (400 microg per day and 800 microg per day) all given once daily for 4 days at each dose via a pressurised metered dose inhaler (pMDI) at 0800 hours. After 4 days of treatment, plasma cortisol was measured at 0800 hours (24 h after the last dose) and a 10-h overnight urine collection was taken, 14 h after the last dose (2200-0800 hours) for analysis of cortisol and creatinine excretion.. Plasma cortisol levels (nmol.l(-1), as geometric mean) at 0800 hours demonstrated a significant difference between the highest doses of FP and BUD (424.1 vs 510.3 nmol.l(-1), respectively) but not between the low doses (506.8 vs 514.9 nmol.l(-1); PL 532.2 nmol.l(-1)). For the highest dose FP (750 microg) this equated to 20% suppression of 0800 hours plasma cortisol. Likewise, for overnight urinary cortisol output (nmol.10 h(-1) as geometric mean), there was a significant difference at the high doses of FP and BUD (25.5 vs 38.2 nmol.10 h(-1)), but not at the low doses 31.3 vs 34.8 nmol.10 h(-1); PL 32.0 nmol.10 h(-1). For the overnight urinary cortisol/creatinine ratio (nmol.mmol(-1), as geometric mean) there was a similar trend; 4.5 vs 6.1 nmol.mmol(-1) for high dose and 5.6 vs 6.3 nmol.mmol(-1) for low dose; PL 5.9 nmol.mmol(-1).. Repeated doses of FP 750 microg once daily caused greater adrenal suppression than BUD 800 microg once daily, when comparing effects on plasma cortisol levels at 0800 hours, 24 h after the last dose, as well as effects on overnight urinary cortisol output. Neither FP 375 microg once daily nor BUD 400 microg once daily produced detectable adrenal suppression.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Cross-Over Studies; Female; Fluticasone; Humans; Hydrocortisone; Male; Single-Blind Method

There are still some concerns about the safety of high doses of inhaled glucocorticosteroids (ICS). We compared the safety and efficacy of fluticasone propionate (FP) and beclomethasone dipropionate (BDP) in 306 patients with moderate to severe asthma in a double-blind, multicenter, cross-over study of 12 mo duration. During the 1-mo run-in period, bronchodilators were replaced by salmeterol 50 microg twice daily, increasing morning peak expiratory flow rate (PEFR) by 28 L/min (p < 0.001) and FEV1 by 6.2% predicted (p < 0.001). At randomization the current ICS was replaced by 500 microg BDP or 250 microg FP in accordance with previously taken 500 microg BDP or 400 microg budesonide (BUD). No significant differences between the two treatments regarding morning plasma cortisol, urinary excretion of calcium and hydroxyproline, FEV1, and PEFR were observed at any time point during the study. Osteocalcin and bone mineral density (BMD) were improved over baseline in the FP group, resulting in higher serum osteocalcin levels (mean difference 0.28 ng/ml; p < 0.001) and higher BMD in the spine (1.0%; p = 0.05), femoral neck (1.6; p < 0.01), and Ward's triangle (3.6%; p = 0.01) as compared with BDP. We conclude that chronic treatment with FP, at half the dose of BDP, results in a similar antiasthma effect but a more favorable safety profile with respect to bone metabolism and mineral density.

Topics: Administration, Topical; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Belgium; Bone Density; Bronchodilator Agents; Budesonide; Calcium; Cross-Over Studies; Double-Blind Method; Female; Femur Neck; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Hydroxyproline; Male; Middle Aged; Osteocalcin; Peak Expiratory Flow Rate; Safety; Salmeterol Xinafoate; Spine

The efficacy and tolerability of fluticasone propionate (FP) 2 mg daily via a metered-dose inhaler and Volumatic (Glaxo Wellcome) spacer device was compared with nebulized budesonide (nBUD), 2 and 4 mg daily, in a multi-centre, open-label, cross-over study of adult asthmatics. Patients received, in random order, either 4 weeks of treatment with FP followed by 4 weeks of treatment with nBUD, or vice versa, with an intervening 4 week 'wash-out' period between treatments. Thirty patients completed the study, of whom 24 were evaluable. In terms of the primary efficacy parameter, change in mean morning peak expiratory flow (PEF) (l min-1) from baseline to the fourth week of each treatment period, FP was more effective than nBUD [mean difference (FP-nBUD) 21.1 l min-1, P = 0.007, 95% CI (6.5, 35.7)]. Sub-group analysis demonstrated FP to be superior to the 4 mg nBUD [mean treatment difference (FP-nBUD) 42.9 l min-1, P = 0.026, 95% CI (7.1, 78.8)] and at least as efficacious as the 2 mg nBUD sub-group [mean treatment difference (FP-nBUD) 10.2 l min-1, P = 0.211, 95% CI (-6.5, 26.9)]. Furthermore, larger reductions in diurnal variation were observed during FP treatment [mean treatment difference (FP-nBUD) -4.4 percentage points, P = 0.028, 95% CI (-8.4, -0.5)]. There was no significant difference between the treatments for the proportion of symptom-free 24 h periods. Of those expressing a preference, significantly more patients found FP via a metered-dose inhaler and spacer device both easier to administer (78%, P = 0.007) and more convenient to take (76%, P = 0.008) than nebulized budesonide. In addition, cost per patient analysis showed that nebulized budesonide was from 1.7 to 3.5 times more expensive than FP.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Budesonide; Costs and Cost Analysis; Cross-Over Studies; Drug Delivery Systems; Fluticasone; Humans; Middle Aged; Nebulizers and Vaporizers; Patient Satisfaction; Peak Expiratory Flow Rate

To determine whether inhaled fluticasone propionate has long-term effects on growth in children with persistent asthma.. In a double-blind, randomized, parallel-group, multicenter study, 325 prepubescent children with persistent asthma and normal growth rates were treated with placebo or inhaled fluticasone propionate powder 50 microg or 100 microg administered twice daily by a breath-actuated device for 1 year. Growth was evaluated monthly, whereas other safety variables and pulmonary function were evaluated periodically.. The prepubescent patients showed no statistically significant differences in mean height, mean growth velocity, or mean skeletal age between any of the treatment groups at any time. Over a period of 1 year, mean height (+/- SE) increased 6.15 +/- 0.17 cm in the placebo group, 5.94 +/- 0.16 cm in the fluticasone propionate 50 microg group, and 5.73 +/- 0.13 cm in the fluticasone propionate 100 microg group (p = 0.308, overall).. Prepubescent children treated with fluticasone propionate 50 microg and 100 microg administered twice daily for 1 year grew at rates similar to placebo-treated control subjects and at rates equal to expected growth velocity for age.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Growth; Humans; Male

Dose-response relationships with inhaled corticosteroids in the treatment of asthma have been difficult to establish. A multicenter, double-blind, parallel-group study was conducted to evaluate the clinical efficacy and safety of low doses of inhaled fluticasone propionate (FP) in patients with mild to moderate asthma. Methacholine challenge testing was conducted in addition to measurement of traditional efficacy variables. After a single-blind screening period, 138 patients > or = 12 years of age were randomly assigned to receive placebo, FP 50 microg, or FP 100 microg, twice daily for 8 weeks. The results of methacholine challenge testing averaged over all visits favored FP 200 microg/day over placebo and FP 100 microg/day (p < 0.05); there were no significant differences between placebo and FP 100 microg/day. Mean changes from baseline to endpoint favored each dose of FP over placebo based on forced expiratory volume in 1 sec (FEV1), patient-measured peak expiratory flow (PEF), total symptom scores, and rescue bronchodilator use (p < 0.05); there were no differences in these parameters between the two doses of FP. The addition of methacholine challenge testing allowed definition of a dose-response relationship that was not apparent with traditional efficacy variables.

Topics: Administration, Inhalation; Administration, Topical; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Methacholine Chloride; Respiratory Function Tests

Antigen processing determines the production of peptides from antigens - including allergens - and their binding to class II major histocompatibility complex molecules, that stimulate T-cell responses. Heat shock protein (hsp) 70 are recognized to have a role in chaperoning antigenic peptides and in facilitating class II peptide assembly. We studied the HLA-DR and hsp70 expression on BAL cells and bronchial biopsies from asthmatics, as well as the effect of low dose fluticasone propionate treatment.. Twenty-three asthmatics and eight normal subjects were selected. In each subject BAL and bronchial biopsies were performed. Eighteen out of 23 asthmatics, underwent the second bronchoscopy after 6 weeks of low dose inhaled fluticasone propionate treatment (250 microg b.d.) in a placebo-controlled double-blind study. BAL fluid and biopsies were processed to evaluate HLA-DR and hsp70 expression by immunochemistry methods.. Hsp70 and HLA-DR upregulation was present on professional and non-professional antigen presenting cells (APCs). In asthmatics, the hsp70 and HLA-DR expression was higher in BAL (hsp70 P<0.001, HLA-DR P<0.001) and bronchial epithelium (hsp70 P<0.001, HLA-DR P<0.001) when compared with controls. We also observed a significant correlation between hsp70 and HLA-DR expression in BAL (P<0.005) and epithelium (P<0.001). Fluticasone propionate treatment down-regulated the hsp70 and HLA-DR expression in BAL (hsp70 P < 0.001, HLA-DR P < 0.05) and bronchial epithelium (hsp70 P < 0.05, HLA-DR P < 0.05). A serial section comparison study showed that CD1a+ cells and macrophages were positive for both hsp70 and HLA-DR in the submucosa.. Our results support the hypothesis that hsp70 over-expression implies a potential role for these proteins in antigen processing and/or presentation resulting in an increased activity of APCs, which is essential for the initiation and modulation of the asthmatic immune response in chronic asthma. Fluticasone propionate induces downregulation of HLA-DR and hsp70 molecules thus regulating inflammation by affecting key mechanisms of the allergic response.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Antigen Presentation; Antigen-Presenting Cells; Asthma; Bronchi; Bronchoalveolar Lavage Fluid; Bronchoscopy; Dendritic Cells; Double-Blind Method; Epithelial Cells; Female; Fluticasone; HLA-DR Antigens; HSP70 Heat-Shock Proteins; Humans; Macrophages; Male; Middle Aged; Up-Regulation

The Diskus/Accuhaler inhaler (D/A) is a new multidose powder inhaler, designed to deliver all asthma drugs. This study was carried out to establish clinical equivalence between FP 250 microg twice daily (b.i.d.) via the D/A and FP 250 microg b.i.d. via the current powder inhaler, the Diskhaler (DH). Also, device handling and patient preference for both devices were determined. This was a multicenter, randomized, double-blind, double-dummy, parallel-group study. Adult asthmatics (364, aged 18-79) requiring inhaled corticosteroids in a daily dosage of 400 microg up to and including 1000 microg and demonstrating a mean morning peak expiratory flow rate (PEFR) calculated from the last 7 days of the run-in of less than 85% of the response after salbutamol, a baseline forced expiratory volume in 1 sec (FEV1) between 50 and 90% of their predicted normal value, and an ability to correctly use both devices, were randomized to a 12-week treatment period. No statistically significant differences between the two devices were seen for mean morning PEFR (p = 0.76), mean evening PEFR (p = 0.88), median daytime and nighttime symptom score (p = 0.57 and p = 0.47), median percentage of rescue-free days and nights (p = 0.43 and p = 0.24), and clinic visit lung function. No differences in the safety profile of FP were seen. Patients found the D/A easier to use and easier with respect to assessing the number of doses remaining (both p < 0.001). Sixty-five percent of the patients expressed an overall preference for the D/A over the DH (p < 0.001). The results show that FP 250 microg b.i.d. via the D/A is clinically equivalent to delivery via the DH. Both treatments proved to be equally safe and were well tolerated. The D/A was easier to use and patients preferred the D/A over the DH.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Patient Satisfaction; Peak Expiratory Flow Rate; Therapeutic Equivalency

Although in the past drug interventions were measured primarily on the basis of their efficacy and safety, today we are increasingly interested in what impact treatments have on the patient's day-to-day activities and quality of life.. We sought to assess the effect of treatment with fluticasone propionate (FP) on functional status and sleep disturbances in children with asthma and to evaluate possible changes in the quality of life of the parents of these children after treatment.. As part of a randomized, double-blind, parallel-group, placebo-controlled, multicenter study on the effects of FP powder (50 or 100 microg twice daily) on growth in children aged 4 to 11 years with mild-to-moderate asthma (n = 325), parents/caregivers completed the following questionnaires at baseline and at weeks 24 and 52 of treatment: Functional Status IIR (FSII), Sleep Scale-Children (SLP-C), and Quality of Life of Parents of Asthmatic Children (QOL-PAC). Change from baseline to weeks 24 and 52 within each treatment group was analyzed by using paired t-tests, and differences between treatment groups were analyzed by using analysis of covariance.. Mean FSII and SLP-C scores improved significantly over baseline values with either 50 or 100 microg FP at weeks 24 and 52 (p < 0.05) and were significantly better than scores in the placebo group (p < 0.05). In contrast, FSII scores at week 52 and SLP-C scores at weeks 24 and 52 decreased significantly in the placebo group (p < 0.05). QOL-PAC results revealed that scores on the Burden scale were significantly improved in both FP groups at weeks 24 and 52. Subjective Norms and Social scales improved significantly only in the 100 microg FP group at week 52.. The results of this study show that FP (either 50 or 100 microg twice a day) was associated with significant improvements in functional status and decreased sleep disturbances in children with asthma. In addition, treatment of children with FP was associated with a decreased burden on the parents of these children with asthma.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Outcome Assessment, Health Care; Parents; Quality of Life; Sleep Wake Disorders; Surveys and Questionnaires

Inhaled corticosteroids are increasingly being used to treat mild-to-moderate asthma in children. However, data regarding therapy with this class of compounds, especially in children under age 6 years, is limited. Fluticasone propionate is a third generation inhaled corticosteroid with an optimal therapeutic index. Few large prospective clinical trials have been conducted to evaluate the efficacy and safety of fluticasone propionate powder in children.. We sought to determine the efficacy and safety of fluticasone propionate powder administered by means of the Diskus and Diskhaler multidose powder inhalers in pediatric patients with persistent asthma.. Fluticasone propionate powder (50 microg or 100 microg twice daily) or placebo was administered by means of the Diskus or Diskhaler inhalers to 437 children (4 to 11 years old) with persistent asthma for 12 weeks in a randomized, double-blind, parallel-group, multi-center trial. Patients were stratified according to whether they were receiving prior treatment with inhaled corticosteroids or cromolyn or beta2-agonists alone.. Fluticasone propionate powder administered by means of Diskus or Diskhaler significantly improved FEV1 (mean increase from baseline of 0.22 to 0.24 L; p < or = 0.023), clinic morning peak expiratory flow (mean increase from baseline of 48 to 55 L/min; p < or = 0.006), patient-measured morning (p < or = 0.001) and evening (p < or = 0.003) peak expiratory flow, and asthma symptom scores (in all but the 50 microg Diskus group; p < or = 0.036), as well as reduced albuterol use (p < or = 0.002) and nighttime awakenings (p < or = 0.019) at endpoint. Efficacy parameters were not significantly different between the two doses with either device. More placebo-treated patients discontinued the study because of lack of efficacy than patients in any fluticasone propionate group (p < 0.001). Fluticasone propionate did not suppress morning plasma cortisol concentrations and did not affect 24-hour urinary free-cortisol excretion. Adverse events were primarily pharmacologic effects of inhaled corticosteroids, and those related to the study drug occurred with low frequency. Patient satisfaction with both the Diskus and Diskhaler devices was high, with a majority of patients (> 80%) rating them favorably.. This study demonstrated that fluticasone propionate powder, at the conventional recommended doses of up to 200 microg/day administered by means of Diskus or Diskhaler, was well tolerated and improved lung function in children even as young as 4 and 5 years old regardless of whether they were previously treated with inhaled corticosteroids or cromolyn or beta2-agonists alone.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Male; Nebulizers and Vaporizers; Pituitary Function Tests; Pituitary-Adrenal System; Respiratory Function Tests

Inhaled glucocorticoids (iGC) have become important first line agents in the management of moderate-to-severe asthma. Severe asthma is associated with reduced glucocorticoid receptor (GCR) binding affinity.. To evaluate the potential impact of inhaled fluticasone propionate on markers of airway inflammation [GCR binding affinity (Kd) and eosinophil cationic protein (ECP)] and oral GC requirements in steroid-dependent asthmatics, we examined the effects of fluticasone propionate (FP) 500 microg or 1000 microg BID and placebo in a double-blind, randomized study of 13 steroid-dependent asthmatics at a single center. Glucocorticoid receptor binding affinity and ECP values were obtained at baseline, 4, 6, 26, and 52 weeks after patients were enrolled into the study. Oral GC dose and FEV1 values were also recorded at each visit.. Inhaled FP resulted in large reductions in oral GC requirement by 6 weeks of therapy while no reduction was seen in the placebo group. All patients in the FP 2000 microg/d group who continued double-blind therapy at 52 weeks were able to eliminate oral prednisone use. In contrast, every patient in the placebo group had to be withdrawn from the study due to poor asthma control. Associated with the oral GC dose reduction on high dose FP therapy, were improvements in GCR binding affinity with the GCR Kd falling from 42.5 nM at baseline to 19.5 nM at 6 weeks (P=.08). The GCR KD values remained stable thereafter with values of 23.5 nM at 26 weeks (P=.02) and 19.5 nM at 52 weeks (P=.01). In addition, high dose FP therapy resulted in reductions in serum ECP values.. This study suggests that high dose FP therapy results in significant oral GC sparing effects associated with improved GCR binding affinity and reductions in serum ECP levels in patients with steroid-dependent asthma.

Topics: Administration, Oral; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Blood Proteins; Double-Blind Method; Eosinophil Granule Proteins; Female; Fluticasone; Glucocorticoids; Humans; Lung; Male; Middle Aged; Receptors, Glucocorticoid; Ribonucleases

Bronchial inflammation plays a central role in asthma. We investigated whether parameters of inflammation were increased in peripheral blood. Furthermore, we tested whether fluticasone propionate (FP), a new inhaled corticosteroid (ICS), and beclomethasone dipropionate (BDP) affected these parameters. FP 750 microg/day and BDP 1500 microg/day were compared in a randomized, crossover study consisting of two 6-week treatment periods, each preceded by a 3-week placebo period. Twenty-one patients with symptomatic asthma completed the study. The results were compared with those of six normal subjects (controls). Immunophenotyping of inflammatory cells was performed in whole blood, and serum eosinophil cationic protein (ECP) was measured. With regard to clinical efficacy, ICS increased PC20 histamine by more than 1.9 doubling doses and FEV1 by more than 0.34 l. The number of CD3/HLA-DR+ lymphocytes was significantly increased in asthmatics compared to the normal subjects, both after placebo (P<0.01) and after therapy (P<0.05). The CD3/HLA-DR+ lymphocytes decreased significantly after treatment with FP (P<0.05). Serum ECP was elevated in patients without ICS and decreased after treatment with BDP (P<0.001). In conclusion, the number of CD3/HLA-DR+ lymphocytes and serum ECP levels were raised in the peripheral blood of symptomatic asthmatics, and decreased by clinically effective doses of ICS. In this respect, FP 750 microg/day was at least as effective as BDP 1500 microg/day.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; CD3 Complex; Cross-Over Studies; Double-Blind Method; Eosinophils; Female; Flow Cytometry; Fluticasone; HLA-DR Antigens; Humans; Leukocyte Common Antigens; Male; Middle Aged; Phenotype; Receptors, Interleukin-2; T-Lymphocytes

1. As mineralocorticoid and adrenocorticoid activity are both under the diurnal control of adrenocorticotropic hormone secretion, we aimed to evaluate whether the normal circadian rhythm of cortisol and aldosterone secretion was suppressed by inhaled corticosteroid therapy.2.Ten normotensive patients with mild-moderate asthma, mean age 24.0 (S.D. 9.8) years and mean arterial pressure 90.7 (9.8) mmHg, were studied in a double-blind, randomized crossover design comparing placebo with fluticasone propionate, 1000 microgram administered twice daily at 08:00 h and 20:00 h. After 5 days of repeated dosing at steady state, measurements were made of plasma cortisol and aldosterone at midnight and 08:00 h.3. With placebo there was a significant (P<0.05) difference between cortisol values at 08:00 h (588.6+/-83.8 nmol/l) and midnight (109.6+/-35.0 nmol/l), whereas after treatment with fluticasone propionate there was no significant difference between levels at 08:00 h (143.3+/-57.4 nmol/l) and midnight (64.3+/-22.3 nmol/l). For cortisol at 08:00 h there was also a significant (P<0.05) difference between placebo and fluticasone propionate. The same pattern was observed for aldosterone. Plasma aldosterone levels at 08:00 h after treatment with placebo (129.6+/-30.9 nmol/l) were significantly different (P<0. 05) to those seen at midnight (40.4+/-6.2 nmol/l). After treatment with fluticasone propionate, there was no significant difference between levels at midnight (55.4+/-11.7 nmol/l) and 08:00 h (64. 8+/-12.7 nmol/l).4. These results show that inhaled corticosteroid therapy abolishes the circadian rhythm of aldosterone and cortisol secretion. This may have possible implications for patients taking inhaled corticosteroids in terms of the beneficial cardiac effects of suppressing early morning aldosterone.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aldosterone; Analysis of Variance; Androstadienes; Anti-Inflammatory Agents; Asthma; Circadian Rhythm; Cross-Over Studies; Depression, Chemical; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male

Mast cells and eosinophils are important cells that contribute to the process of inflammation in asthma either by activating other cells or by secreting products which are potentially toxic to the respiratory epithelium. The influx of these cells in the airways and the secretion of toxic products by these cells is abrogated by inhaled corticosteroids.. In a double blind randomised, placebo controlled, study in children with stable moderate asthma (N = 34, 15 children received fluticasone propionate (FP), an inhaled corticosteroid, and 19 children used a placebo), we investigated the influence of treatment with FP 100 microg b.d. on various parameters of inflammation: number of eosinophils, secretory products of eosinophils i.e. ECP and EDN (in serum and urine) and a secretory product of mast cells, histamine, which is determined as the compound to which histamine is converted and excreted by the human body: NT-methyl-histamine.. Previously we reported that lung function increased and bronchial hyperresponsiveness decreased in the 30 children that completed the study during treatment with FP. In these children we found that none of the laboratory parameters of inflammation changed significantly during treatment with either FP or placebo. However, the decrease in urinary EDN almost reached significance (P = 0.07).. Our results indicate that the number of eosinophils, serum ECP and EDN and urinary EDN as well as urinary NT-methyl-histamine do not reflect asthma disease activity in children with stable moderate asthma. Our data on urinary EDN warrant further study of the use of this parameter to monitor asthma in children.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Inflammatory Agents; Asthma; Blood Proteins; Bronchial Hyperreactivity; Child; Double-Blind Method; Eosinophil Granule Proteins; Eosinophil-Derived Neurotoxin; Eosinophils; Female; Fluticasone; Humans; Immunoglobulin E; Inflammation Mediators; Male; Mast Cells; Methylhistamines; Proteins; Respiratory Function Tests; Ribonucleases

Previous studies have suggested a 2:1 efficacy advantage of fluticasone propionate (FP) over beclomethasone dipropionate (BDP) in adults on high dose inhaled steroids and children on low dose inhaled steroids. The lower doses of FP required to provide equivalent efficacy to BDP also appear to have fewer systemic effects as measured by adrenal function.. The efficacy and safety of FP 750 micrograms/day and BDP 1500 micrograms/day were compared in 30 children with persistent asthma (requiring 1000-2000 micrograms/day of inhaled corticosteroids) in a 12 week randomised double blind crossover study. Medication was delivered by a spacer device in two divided doses. Primary efficacy variables were peak expiratory flows (PEF). Adrenal function was assessed by 24 hour urinary free cortisol levels at eight and 12 weeks and ACTH and low dose synacthen tests (LDST) at 12 weeks. The results were adjusted for sequence and period differences.. There was no difference in the primary efficacy variables over the two 12 week treatment periods (difference in adjusted means for morning PEF 1.3 l/min (95% CI -6.1 to 8.8), p = 0.112) and symptom scores (cough, tachypnoea, wheeze, shortness of breath; difference in adjusted means of night time scores: -0.06 (95% CI -0.14 to 0.03); p = 0.136). Similar degrees of mild adrenal dysfunction were found during BDP and FP treatment phases. Identical height gain velocities were shown during the corresponding periods.. FP 750 micrograms/day is as effective as BDP 1500 micrograms/day in children with persistent asthma. At these very high doses we were unable to demonstrate a safety advantage of FP over BDP as assessed by adrenal function. However, measures of adrenal function may have been influenced by concurrent and previous systemic steroid usage, and possibly by effects of disease activity.

Topics: Administration, Inhalation; Adolescent; Adrenal Glands; Adrenocorticotropic Hormone; Analysis of Variance; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Hydrocortisone; Male

There is a dearth of data on long-term effects of inhaled corticosteroids (ICS) on bone architecture in childhood asthma. This study was designed to assess the possible effects of two different inhaled steroids on bone mineral density (BMD) in steroid-naïve, prepubertal children. Twenty-three children were randomized to receive equipotent doses of either fluticasone propionate (100 micrograms twice daily) or beclomethasone dipropionate (200 micrograms twice daily). They were followed up over a period of 20 months with regular dual-energy X-ray absorptiometry scans for BMD. Densitometry of lumbar spine and total body showed a significant increase over time, which followed the normal patterns for growth. No difference was observed between the two subgroups. There was no change in fat distribution over time and no increase in percentage total body fat. As expected, girls had significantly higher total body fat. This absence of deleterious effects suggests that in the standard doses used neither beclomethasone nor fluticasone has any significant effect on bone density over a moderate period of time. Further studies should continue monitoring BMD through the critical years of bone mass accumulation during adolescence.

Topics: Absorptiometry, Photon; Adipose Tissue; Administration, Topical; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bone Density; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Follow-Up Studies; Glucocorticoids; Humans; Lumbar Vertebrae; Male

Inhaled corticosteroids are the most widely used treatment for asthma, a disease characterised by both functional and immunopathological abnormalities. This study investigated the relative effects of inhaled corticosteroids on these two features of asthma over time.. A randomised, double blind, placebo controlled, parallel group study with inhaled fluticasone propionate, (FP 2 mg daily) was conducted in 27 patients with asthma. Following baseline analysis, the study tested the effects of short term (two weeks) and longer term (eight weeks) treatment. At each time point (0, 2, and 8 weeks) lung function tests were performed and endobronchial biopsy specimens obtained to determine the distribution and number of lymphocyte, macrophage and eosinophil subsets using immunohistological analysis. Twenty three patients completed the study, 11 on FP and 12 placebo.. FEV1, delta FEV1, FEF25-75, and FEV1/FVC all improved after two weeks of FP treatment. This improvement was maintained but not increased after eight weeks. PC20FEV1 showed a trend to increase but was not significantly improved at eight weeks. No significant changes were seen in the placebo group. The numbers of T cells, macrophages, and eosinophils in the bronchial wall were reduced by two weeks of treatment with FP but were unaltered by placebo. The improvement offered by FP continued over the eight week period. Reductions in CD4:CD8 ratio and numbers of activated (EG2+) eosinophils were only significant after eight weeks of treatment.. These results reveal that FP influences both functional and immunopathological parameters of asthma. Temporal relationships suggest that these are parallel but not necessarily interrelated effects. While short term treatment is effective in "normalising" the functional abnormalities in asthma, the impact of FP on bronchial inflammation appears to be progressive, taking up to eight weeks and more.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchoscopy; CD4-CD8 Ratio; Double-Blind Method; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Immunohistochemistry; Macrophages; Male; Middle Aged; T-Lymphocytes

In a previous single dosing comparison between fluticasone propionate and budesonide differences in cortisol levels measured at 08.00 hours were observed at doses in excess of 1000 micrograms. The aim of this study was to compare the adrenal suppression caused by chronic twice daily dosing with inhaled fluticasone propionate (FP) and budesonide (B) given on a microgram equivalent basis by metered dose inhaler to asthmatic patients.. Twelve stable asthmatic patients of mean age 29.7 years with forced expiratory volume in one second (FEV1) 89.0% predicted and mid forced expiratory flow (FEF25-75) 58.9% predicted, on 400 micrograms/day or less of inhaled corticosteroid, were studied in a double blind, placebo controlled, crossover design comparing inhaled budesonide and fluticasone propionate in doses of 250 micrograms, 500 micrograms, and 1000 micrograms twice daily. Each dose was given at 08.00 hours and 22.00 hours for four days by metered dose inhaler with mouth rinsing. Measurements were made of overnight urinary cortisol excretion and plasma cortisol levels at 08.00 hours, 10 hours after the eighth dose.. The plasma cortisol levels (nmol/ l) at 08.00 hours showed that fluticasone propionate produced lower cortisol levels than budesonide at all three dose levels: F500 333.8, B500 415.2 (95% CI 28.9 to 134.0); F1000 308.3, B1000 380.3 (95% CI 10.5 to 133.5); F2000 207.3, B2000 318.5 (95% CI 5.8 to 216.7); placebo 399.9. Fluticasone produced greater effects than budesonide on the overnight urinary cortisol/creatinine ratio (nmol/mmol) at all three dose levels: F500 3.12, B500 5.55 (95% CI 0.16 to 3.79); F1000 2.54, B1000 6.12 (95% CI 1.25 to 5.91); F2000 2.07, B2000 6.09 (95% CI 0.88 to 7.18); placebo 5.23.. With repeated dosing across a dose range of 250-1000 micrograms twice daily, fluticasone propionate produced significantly greater adrenal suppression than budesonide for both plasma and urinary cortisol. It was therefore possible to demonstrate differences between fluticasone and budesonide at lower doses with chronic dosing from those previously found with single dosing when given on a microgram equivalent basis in asthmatic patients. Factors contributing to the systemic adverse activity profile of fluticasone comprise enhanced receptor potency, prolonged receptor residency time, greater tissue retention, and a longer elimination half life.

Topics: Adrenal Glands; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Creatinine; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Pregnenediones

Inhaled corticosteroids have been shown to effectively reduce large circadian fluctuations in peak expiratory flow (PEF). Salmeterol xinafoate (SLM), a new long-acting beta2-agonist being used in the treatment of nocturnal airway obstruction, has proved to be very effective in this respect as well. However, it is yet unknown whether using SLM alone or in combination with fluticasone propionate (FP) constitutes the best treatment. We studied, in a randomized, double-blind, parallel manner, 46 asthmatics with increased circadian variation in PEF (> or = 15%) for 6 wk to compare FP 250 microg, SLM 50 microg, and a combination of them, all given twice a day. These three treatment protocols were equally effective in improving the generally used clinical outcome parameters, i.e., the circadian variation in PEF and FEV1 and bronchial hyperresponsiveness (BHR) to methacholine (MCh) during the day and at night. FEV1 increased more at 4:00 A.M. than at 4:00 P.M. (FEV1 at both time points > 90% predicted). BHR to MCh improved with at least 1.5 doubling concentrations, thereby reducing the significant nocturnal decline in the SLM and FP group, but not in combination. The improvement in BHR to adenosine 5'monophosphate was greater (p = 0.05) when FP was combined with SLM but not when FP or SLM were used alone. Our data support the clinical view that FP, with its anti-inflammatory capacity, has greater beneficial effects as monotherapy than does SLM. However, this was detectable only by using the "indirect" stimulus adenosine 5'monophosphate, which is more specific in assessing changes in different components of airway wall inflammation than is MCh.

Topics: Adenosine Monophosphate; Administration, Inhalation; Administration, Topical; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Circadian Rhythm; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Glucocorticoids; Humans; Male; Methacholine Chloride; Salmeterol Xinafoate

Fluticasone propionate, an inhaled corticosteroid with negligible systemic bioavailability via the oral route, is efficacious in the treatment of asthma when administered via metered-dose inhaler.. To evaluate the efficacy and safety of inhaled fluticasone propionate powder in patients with moderate asthma previously treated with an inhaled corticosteroid.. This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of 342 adolescent and adult patients with moderate asthma [forced expiratory volume in 1 second (FEV1) between 50% and 80% of predicted] treated previously by beclomethasone dipropionate or triamcinolone acetonide. Patients received fluticasone propionate powder 50 micrograms, 100 micrograms, 250 micrograms, or placebo via a breath-actuated inhalation device, the Diskhaler, twice daily for 12 weeks.. Patients in the fluticasone propionate groups experienced a mean increase from baseline to endpoint in FEV1 ranging from 0.43 L to 0.47 L. Patients in the placebo group experienced a mean decrease from baseline of 0.22 L (P < .001). The probability of patients remaining in the study over time without developing signs of exacerbating asthma was significantly greater in the fluticasone propionate groups than in the placebo group (P = .001). Asthma symptom scores, supplemental rescue albuterol use, and number of nighttime awakenings due to asthma requiring treatment also improved significantly with all fluticasone propionate treatment regimens compared with placebo (P < .001). There were no statistically significant differences at endpoint among the three fluticasone propionate groups. No serious drug-related adverse events occurred.. Fluticasone propionate powder (50, 100, and 250 micrograms) was well-tolerated and significantly improved lung function in patients with moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Circadian Rhythm; Double-Blind Method; Female; Fluticasone; Humans; Male; Placebos; Powders; Respiratory Function Tests

A 6 week randomised, multicentre parallel group study compared the efficacy and safety of fluticasone propionate (FP) dry powder inhaler 2 x 250 micrograms/d and flunisolide (FLUN) metered dose inhaler 2 x 500 micrograms/d. 169 patients with mild to moderate asthma (FEV1/VC > or = 60% predicted) participated. The final clinical judgement resulted from the change in FEV1 and symptom intensity (measured by the oxygen cost diagram = OCD). 79% of the patients in the FP group showed improvement or partial improvement, compared to 57% in the flunisolide group (p = 0.02). The results indicate a greater efficacy of FP concerning the intensity of dyspnea, cough and symptoms at night (p = 0.03). During the treatment period morning and evening PEF improved in both groups; in 81% of the FP patients and 71% of the FLUN patients. 50% of all patients had a FEV1 below 2.5 l/s. The greater efficacy of FP was especially found in patients with lower FEV1. In both treatment groups drug safety was judged good or excellent by most patients. The results of this 6 week study indicate a greater efficacy (FEV1 and symptoms) of FP 2 x 250 micrograms/d versus FLUN 2 x 500 micrograms/d. The study confirms that there is at least a 2:1 ratio in efficacy comparing FP with FLUN in asthma patients.

Topics: Adolescent; Aerosols; Aged; Aged, 80 and over; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Female; Fluocinolone Acetonide; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Powders; Respiratory Hypersensitivity; Treatment Outcome

Because biological indicators alone do not adequately represent the comprehensive health status of a patient with asthma, we also assessed patients' health-related quality of life (HRQOL) in a randomized, double-blind, placebo-controlled study of the effects of the inhaled corticosteroid fluticasone propionate (FP). A total of 342 patients with moderate asthma were treated twice daily for 12 weeks with FP powder (50, 100, or 250 micrograms) or placebo. At regular intervals, patients completed the Medical Outcomes Study Short Form-36, acute version (SF-36A), a general health status questionnaire measuring eight dimensions of HRQOL; the 20-item Living with Asthma (LWA-20) questionnaire, a disease-specific instrument measuring HRQOL; and three additional questions related to sleep loss and number of nighttime awakenings. Each of the three FP groups compared with placebo had significantly higher scores at study endpoint on the Physical Functioning (p < 0.001) and Role-Physical (p < or = 0.0001) dimensions of the SF-36A; the FP 100- or 250-micrograms groups compared with placebo also had significantly higher scores on General Health Perceptions (p < 0.03), Vitality (p < 0.007), and Mental Health (p < 0.02). At endpoint, all three FP groups compared with placebo had significantly better scores on the LWA questionnaire (p < 0.05) and on the sleep-related items (p < 0.0001). These data, collected using both a general health status questionnaire and an asthma-specific questionnaire, demonstrate that fluticasone propionate powder can improve HRQOL in patients with mild-to-moderate asthma.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Powders; Quality of Life

The degree of patient comfort and satisfaction with an inhaler can have an important effect on compliance with asthma treatment and, hence, therapeutic success. The objective of this study was to assess, from the patient's perspective, the importance of various inhaler characteristics and then evaluate patient satisfaction with a new breath-actuated powder inhaler (Diskhaler) based on those characteristics. Self-administered patient satisfaction questionnaires were completed as part of a randomized, double-blind, placebo-controlled study of fluticasone propionate powder in the treatment of asthma. At baseline, patients rated the importance of five inhaler characteristics (convenient to carry, durability, easy to load, easy to hold and operate, and easy to clean). Following exposure to the Diskhaler over a period of 8 weeks, patients rated the inhaler on those same characteristics. They also rated their comfort using the inhaler and their overall satisfaction with the inhaler. Data were available from 274 patients, the majority of whom expressed a high or very high level of satisfaction with the Diskhaler on each of the five characteristics. These ratings were congruent with their ratings of the importance of those same characteristics; 80-90% rated "convenient to carry," "durability," "easy to load," and "easy to hold and operate" as important or very important characteristics for an inhaler, while "easy to clean" was considered somewhat less important, with 63% rating this characteristic as important or very important. Following the initial exposure to the Diskhaler, 67% of patients were comfortable or very comfortable with the inhaler; that percentage increased to 79% after 8 weeks of use. Following 2 and 8 weeks of use, 61 and 62%, respectively, were satisfied or very satisfied with the Diskhaler. In general, satisfaction ratings were not affected by treatment, indicating that patients were evaluating only the inhaler and not the efficacy of the study drug they received. This study helped to identify which selected inhaler characteristics are most important to patients with asthma. The Diskhaler inhaler performed well on those characteristics deemed important to the patients. From their first exposure to the Diskhaler, patients were comfortable using the device, and this overall acceptance of the inhaler was maintained throughout the study.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Double-Blind Method; Fluticasone; Humans; Nebulizers and Vaporizers; Patient Satisfaction; Powders

In a double-blind, parallel-group study, we examined the effect of short-term treatment with inhaled fluticasone propionate (FP) in a group of 20 nonsmoking asthmatic patients who required only beta2-agonists to control their symptoms. We administered FP (250 microg twice daily) or matched placebo for 6 wk. Methacholine challenge was performed before treatment, after 3 wk, and at the end of treatment. Each patient underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy before and after treatment. Eight patients in the placebo group and nine patients in the FP group completed the study. Bronchial responsiveness to methacholine decreased significantly only after 6 wk of treatment with FP (p < 0.05). When we compared the FP group with the placebo group, we observed a significant decrease only in the number of cells expressing intracellular adhesion molecule-1 (ICAM-1) and MAC-1 (p < 0.04 and p < 0.03, respectively). Moreover, we saw that the tryptase level in BAL decreased (p < 0.001), whereas the eosinophil cationic protein (ECP) level did not change significantly. Additionally, the number of eosinophils and mast cells in the lamina propria in bronchial biopsies specimens was significantly smaller in the FP group than in the placebo group (p < 0.02 and p < 0.01, respectively). Additionally, in the FP group, we found that basement-membrane thickness was significantly decreased when compared with that of the placebo group (p < 0.05). In conclusion, our results show that short-term treatment with low-dose FP reduces inflammatory cell infiltration into the lamina propria in bronchial biopsy specimens. Moreover, short-term low-dose FP treatment might control the intensity of airway remodeling in mild asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchi; Bronchitis; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Lung; Male; Methacholine Chloride; Middle Aged; Placebos; Time Factors

To investigate effects on adrenal function of fluticasone, a recently released inhaled steroid preparation with lower systemic bioavailability than beclomethasone dipropionate.. 34 children on high doses (400-909 micrograms/m2/d) of inhaled beclomethasone dipropionate or budesonide were recruited into a double blind, crossover study investigating the effects on adrenal function of beclomethasone and fluticasone propionate, given using a standard spacer (Volumatic). The 24 hour excretion rates of total cortisol and cortisol metabolites were determined at baseline (after a two week run in), after six weeks treatment with an equal dose of beclomethasone, and after six weeks of treatment with half the dose of fluticasone, both given through a spacer device.. The comparison of effects between fluticasone and beclomethasone during treatment periods, although favouring fluticasone in all measured variables, reached significance only after correction for urinary creatinine excretion (tetrahydrocortisol and 5 alpha-tetrahydrocortisol geometric means: 424 v 341 micrograms/m2/d). The baseline data showed adrenal suppression in the children taking beclomethasone (total cortisol geometric means: 975 v 1542 micrograms/d) and a dose related suppression in the children taking budesonide. Suppressed adrenal function in the children who were taking beclomethasone at baseline subsequently improved with fluticasone and beclomethasone during treatment periods.. Fluticasone is less likely to suppress adrenal function than beclomethasone at therapeutically equivalent doses. The baseline data also support the claim that spacer devices should be used for the administration of high doses of inhaled topical steroids.

Topics: Administration, Topical; Adolescent; Adrenal Glands; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Nebulizers and Vaporizers; Peak Expiratory Flow Rate

New inhaled glucocorticosteroids and inhalers are being developed. Their clinical equipotency is difficult to assess and is often discussed.. This study was carried out to compare the effect of budesonide Turbuhaler and fluticasone propionate (FP) Diskhaler in a dose reduction study in children (ages 5 to 16 years) with asthma.. Children treated with budesonide administered through a pressurized metered-dose inhaler with a large volume spacer had their budesonide dose gradually reduced to define the minimal effective dose with this delivery system. After this period, 217 children were randomly allocated to treatment with half the dose of either budesonide Turbukaler or FP Diskhaler for 5 weeks in a double-blind trial. If no deterioration in asthma control was seen, the dose was further reduced by 50% at 5-week intervals until deterioration in asthma control was seen. Throughout the study, morning and evening peak expiratory flow, symptoms, and use of rescue beta 2-agonist were recorded in diaries. Lung function tests and a standardized exercise test were performed at the clinic at the end of each treatment period. Urine cortisol excretion (24 hours) was measured before and after the first 5-week treatment period. Standardized criteria for deterioration in asthma control, based on diary card variables and exercise testing, were used to determine the minimal effective dose for each patient; and from this, the number of dose reduction steps was calculated.. No statistically significant difference was seen in number of dose reduction steps from baseline or in minimal effective dose between the two treatments; mean reduction was 1.59 dose steps for budesonide Turbuhaler and 1.65 dose steps for FP Diskhaler (p = 0.52), and minimal effective dose was 188 micrograms for budesonide Turbuhaler and 180 micrograms for FP Diskhaler. After these dose reductions, the same level of asthma control was observed in the budesonide Turbuhaler and FP Diskhaler groups. Furthermore, no statistically significant differences between the two inhaler-drug combinations were seen in daytime or nighttime symptoms, morning and evening peak expiratory flow, use of rescue beta 2-agonist, lung functions at the clinic, exercise-induced fall in lung function, or 24-hour urinary cortisol excretion during the first 5-week period.. Microgram for microgram, budesonide Turbuhaler and FP Diskhaler are equally effective in treatment of children with moderate asthma.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Aerosols; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Hydrocortisone; Male; Medical Records; Patient Compliance; Pregnenediones

Few thorough comparisons of the systemic effects of inhaled corticosteroids in children are available. The aim of this study was to compare the effect of budesonide and fluticasone propionate on short-term lower leg growth. Fluticasone propionate, budesonide and placebo were administered for 2 weeks in a randomized, double-blind, double-dummy, cross-over design. Twenty four children aged 6-12 yrs received 200 microg x day(-1) of each drug, or placebo. Another 24 children aged 6-12 years received 400 microg x day(-1) of each drug, or placebo. Dry powder inhalers were used. Lower leg length was measured by knemometry twice a week during all three treatment periods, and 24 h cortisol excretion in the urine was measured at the end of each period. In the low-dose group, lower leg growth rate was the same during treatment with placebo (0.35 mm x week(-1)), fluticasone propionate (0.38 mm x week(-1)) or budesonide (0.26 mm x week(-1)). No significant difference (p=0.39) in lower leg growth rate was found between treatment with 400 microg x day(-1) budesonide (0.30 mm x week(-1)) and 400 microg fluticasone propionate treatment (0.37 mm x week(-1)). Growth rate during treatment with budesonide, 400 microg x day(-1), was significantly lower than during placebo treatment (0.52 mm x week(-1)). Cortisol excretion in the urine during treatment with 200 microg x day(-1) fluticasone propionate was significantly reduced as compared with placebo (p=0.006), but not when compared with 200 microg x day(-1) budesonide (p=0.07). Budesonide 200 microg x day(-1) was not significantly different from placebo. Fluticasone propionate and budesonide, both at 400 microg x day(-1), resulted in a significant reduction in cortisol excretion in the urine as compared with placebo (p=0.001). It is concluded that, dose-for-dose, budesonide Turbuhaler and fluticasone propionate Diskhaler have similar systemic effects.

Topics: Administration, Inhalation; Administration, Topical; Aerosols; Androstadienes; Anthropometry; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Growth; Humans; Hydrocortisone; Leg; Male; Pregnenediones

We performed a double-blind, crossover, placebo-controlled study on the effect of fluticasone propionate (FP) treatment on chronic eosinophilic rhinosinusitis in 15 patients with aspirin-induced asthma (AIA). There were 10 women and five men aged 32-60 years; average: 45 years. After a 10-day run-in period, patients underwent two 4-week treatment courses (FP vs placebo), separated by a 2-week washout interval. Clinical activity of FP was evaluated by daily measurement of peak nasal inspiratory flow (PNIF) and a scoring system of subjective symptoms. Nasal challenges with E-lysine aspirin, using active anterior rhinomanometry, were performed at the entry and on the last day of each treatment period. Weekly mean values of symptom scores were generally lower and PNIF measurements higher during treatment with FP than with placebo. This difference was statistically significant for most recorded parameters for the whole 4-week FP treatment. On average, the reactions evoked by aspirin nasal challenge were significantly shorter and milder after treatment with FP than with placebo. In 8/13 patients, FP completely prevented aspirin-precipitated nasal reaction, whereas protection after placebo was observed in only 2/12 subjects (P = 0.004). We conclude that intranasal FP is an effective therapy for chronic eosinophilic rhinitis in patients with AIA.

Topics: Administration, Intranasal; Adult; Androstadienes; Anti-Allergic Agents; Aspirin; Asthma; Chronic Disease; Cross-Over Studies; Double-Blind Method; Eosinophilia; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Provocation Tests; Rhinitis

The objective of this study was to determine whether the therapeutic benefits of inhaled fluticasone propionate are mediated through topical or systemic effects. Two hundred seventy-four patients with asthma receiving beclomethasone dipropionate or triamcinolone acetonide during a 2-wk, single-blind, run-in period were randomized to inhaled fluticasone propionate powder 100 or 500 micrograms twice daily, oral fluticasone propionate 20 mg once daily, or placebo during a 6-wk treatment period. Patients receiving inhaled fluticasone propionate had a significantly greater probability of remaining in the study over time compared with patients receiving oral fluticasone propionate or placebo (p = 0.001). FEV1 and PEF rates at end point were significantly higher with inhaled fluticasone propionate treatment regimens than with oral fluticasone propionate (with the exception of PEF rates for inhaled fluticasone propionate 100 micrograms) or placebo treatments (p < or = 0.004). Systemic exposure to fluticasone propionate as assessed by trough plasma concentrations and/or 12-hr plasma concentration area under the curve analyses (AUC12) was higher with the oral fluticasone propionate than with the two inhaled fluticasone propionate treatment groups. The results of this study suggest that the therapeutic benefits of inhaled fluticasone propionate are mediated through topical effects in the lungs and not through systemic effects.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Biological Availability; Double-Blind Method; Drug Monitoring; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate

The aim of this study was to compare accurately measured growth over 12 months in asthmatic children treated with either fluticasone propionate (FP) 50 micrograms twice daily (b.i.d.) or sodium cromoglycate (SCG) 20 mg four times daily (q.i.d.). After a 2-week run-in, asthmatic children aged 4-10 years from 15 UK centers were randomized in a 3:4 ratio to open-label FP (n = 52) or SCG (n = 70). After 8 weeks, those whose asthma was not adequately controlled were switched from SCG to FP or withdrawn. Standing height was measured (Holtain stadiometry) at baseline, after 8 weeks and at 6 weeks intervals thereafter for 1 year. Morning peak flows (PEFam) were recorded by patients for 2 weeks during baseline, and 1 week before each visit during treatment. Urinary free cortisol (24 h) was measured at baseline, 6 months, and 1 year. After 8 weeks, 22 patients were withdrawn from SCG group (and were switched to FP), and five patients were withdrawn from the FP group due to poor asthma control. A further 21 and 11 patients were withdrawn from the SCG and FP groups, respectively, during the course of the study. There were no significant differences between patients who received FP and SCG for 1 year (n = 34 and n = 26, respectively) in terms of height velocity adjusted for age and gender (HV), or height velocity standard deviation scores adjusted for gender (HVSDS). Mean HV (mean HVSDS) were 6.0 cm/yr (0.1) and 6.5 cm/yr (0.5) for FP and SCG, respectively. There were no treatment differences in mean 24 h urinary free cortisol levels at 6 and 12 months. Mean % predicted PEFam improved over 1 year in both groups but to a greater degree in the FP group. We concluded that growth was normal in mildly asthmatic children receiving FP (50 micrograms bid) for 1 year. There were fewer withdrawals and lung function improved to a greater extent in FP treated patients than in patients receiving SCG.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Body Height; Child; Child, Preschool; Cromolyn Sodium; Drug Administration Schedule; Female; Fluticasone; Growth; Humans; Hydrocortisone; Male; Time Factors

In a previous single dosing study in asthmatic school children fluticasone propionate produced significantly greater suppression of overnight urinary cortisol excretion than budesonide at high doses of 800 micrograms/day or greater. The aim of this study was to assess whether conventional lower doses of both drugs cause adrenal suppression when given at steady state twice daily by large volume spacer on a microgram equivalent basis in asthmatic school children.. Eight school children of mean age 12.1 years with stable asthma of mild to moderate severity (forced expiratory volume in one second (FEV1) 78.6% predicted, mid forced expiratory flow rate (FEF25-75) 72.5% predicted), on 400 micrograms/day or less of inhaled corticosteroid, were studied in a single blind (investigator blind), placebo controlled, crossover design comparing inhaled budesonide and fluticasone propionate 100 micrograms bid and 200 micrograms bid. Each dose was given at 08.00 hours and 20.00 hours for four days by metered dose inhaler via their respective large volume spacers with mouth rinsing. Measurements were made of overnight urinary cortisol and creatinine excretion after the eighth dose.. Neither drug produced significant suppression of overnight urinary cortisol or cortisol/creatinine excretion compared with pooled placebo and there were no differences between the drugs. Only one subject with each drug at 200 micrograms twice daily had abnormally low urinary cortisol excretion of < 10 nmol/12 hours. Ratios for the fold difference between active treatment versus placebo for urinary cortisol excretion were (as means and 95% confidence intervals for difference): budesonide 100 micrograms b.i.d 1.03 (95% CI 0.46 to 1.61), budesonide 200 micrograms b.i.d 1.04 (95% CI 0.62 to 1.46); fluticasone 100 micrograms b.i.d 1.11 (0.45 to 1.77), fluticasone 200 micrograms b.i.d 1.12 (0.78 to 1.47). Likewise, there were no significant differences in overnight urinary cortisol/creatinine excretion.. With repeated twice daily administration at steady state across a dose range of 200-400 micrograms/day no evidence of significant adrenal suppression was found using the sensitive marker of overnight urinary cortisol excretion for either fluticasone propionate or budesonide given via a large volume spacer. These results emphasise the good safety profile in children of these inhaled steroids at conventional dose levels, which have proven antiasthmatic efficacy.

Topics: Adrenal Cortex; Analysis of Variance; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Creatinine; Cross-Over Studies; Drug Administration Schedule; Drug Delivery Systems; Fluticasone; Humans; Hydrocortisone; Nebulizers and Vaporizers; Single-Blind Method

Attempts to delineate efficacy and safety differences among inhaled corticosteroids have been difficult because of the lack of well-controlled, comparative studies reported in the medical literature.. A randomized, double-blind, double-dummy study was conducted in 24 outpatient centers. A total of 291 male and female patients at least 12 years of age with asthma (FEV1 between 50% and 80% of predicted value), who had previously received maintenance therapy with beclomethasone dipropionate or triamcinolone acetonide, were switched to treatment with fluticasone propionate powder (250 microg twice daily), triamcinolone acetonide aerosol (200 microg four times daily), or placebo for 24 weeks.. Mean increase in FEV1 from baseline to end point was significantly (p = 0.009) greater in patients switched to treatment with fluticasone compared with patients switched to treatment with triamcinolone (0.27 L and 0.07 L, respectively). At end point, mean increase in morning peak expiratory flow from baseline was 21 L/min with fluticasone compared with mean decreases of 6 L/min and 28 L/min with triamcinolone and placebo, respectively (p < 0.001 vs triamcinolone and placebo). Supplemental rescue albuterol use decreased by 30% from baseline with fluticasone (p < 0.05 vs triamcinolone and placebo) compared with triamcinolone (6%) or placebo (increased by 50%). The percentage of patients withdrawn from the study because they met predefined lack-of-efficacy criteria was higher with placebo (60%) and triamcinolone (27%) than with fluticasone (17%). Incidence of adverse events and low morning plasma cortisol concentrations were similar across treatment groups except for oral candidiasis (p = 0.035, fluticasone vs placebo).. Fluticasone propionate powder twice daily (500 microg/day) was superior in efficacy to triamcinolone acetonide aerosol four times daily (800 microg/day) in patients with persistent asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosols; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Chronic Disease; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Placebos; Powders; Triamcinolone Acetonide

It has been shown that asthmatics have nocturnal symptoms associated with impaired cognitive performance. We explored more carefully different therapeutic approaches on this performance in relation to lung function in 46 atopics with mild to moderate asthma and with a circadian variation in peak expiratory flow (PEF) > or = 15%. In a double-blind, parallel study they inhaled salmeterol 50 microg or fluticasone 250 microg or a combination of both twice daily for 6 wk. The psychometric tests used informed about focused attention, mental flexibility, concentration, and attention. The results of the psychometric tests were compared with those in healthy control subjects. The PASAT score and the finishing time of the color-word chart subtest were significantly lower in these asthmatics than in the control subjects. Circadian PEF variation was the only independent factor significantly associated with impaired cognitive performance before the treatment period. The three treatment groups were equally effective in reducing circadian PEF variation below 10% and in improving FEV1 and bronchial hyperresponsiveness to methacholine (MCh) both day and night. After 6 wk of therapy, the daytime cognitive performance was improved to levels comparable to those of the healthy control subjects no matter which drug was inhaled. We conclude that a high level of circadian PEF variation (> or = 20%) has been associated with lower daytime cognitive performance in asthmatics. Reduction of circadian PEF variation to below 10% is an important goal of treatment in asthmatics.

Topics: Administration, Inhalation; Adult; Airway Obstruction; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Circadian Rhythm; Cognition; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Peak Expiratory Flow Rate; Psychometrics; Salmeterol Xinafoate; Treatment Outcome

A single blind randomized crossover trial was performed comparing placebo (PL); low (L), medium (M) and high (H) doses of fluticasone propionate (FP) L: 330 microg, M: 770 microg, H: 1,540 microg per day and triamcinolone acetonide (TAA) L: 400 microg, M: 800 microg, H: 1,600 microg per day. Each drug was given twice daily over a total of 9 d, with 3 d for each dose level. Each 9-d drug sequence was preceded by a 3-d placebo, and was separated by a 12-d washout period. Twelve mild-to-moderate, stable adult asthmatics, mean (SEM) age, 34.3 (2.9) yr, mean FEV1: 82.1 (2.0) % predicted, and FEF25-75%: 53.6 (5.5) % predicted, receiving up to 400 microg of inhaled corticosteroid per day, were studied. After each 3-d treatment period, blood samples were taken for 8:00 A.M. serum cortisol. Ten-hour overnight urine collections were taken for measurement of urinary cortisol and corrected for creatinine excretion, starting at 10:00 P.M. following the sixth dose. For 8:00 A.M. serum cortisol compared with PL there was significant (p < 0.001) dose-related suppression with FP but not with TAA, which amounted to a 2.03-fold ratio for H FP versus H TAA. For corrected urinary cortisol/creatinine excretion, there was a significant (p < 0.005) dose-related suppression for FP but not for TAA. This amounted to a 1.9-fold ratio for H FP versus H TAA. For doses < 1,000 microg/d, the number of individual results with an abnormal low urinary cortisol value (< 10 nmol/10 h) were: 10/24 for FP versus 3/24 for TAA (p < 0.005). In conclusion, for 8:00 A.M. serum cortisol and overnight corrected urinary cortisol/creatinine excretion, there was significant dose-related suppression with FP but not with TAA. For both of these parameters at the highest dose of both drugs, this amounted to a two-fold ratio in suppression.

Topics: Administration, Inhalation; Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluticasone; Forced Expiratory Flow Rates; Humans; Hydrocortisone; Male; Predictive Value of Tests; Regression Analysis; Single-Blind Method; Triamcinolone Acetonide

We have previously demonstrated that a single dose of oral prednisolone but not single doses of inhaled fluticasone had facilitatory effects on lymphocyte beta2-adrenoceptor (AR) function. To address possible differences in steady-state time-course, the aim of this study was to determine if repeated dosing with inhaled fluticasone would have facilitatory effects on lymphocyte beta2-AR. Plasma cortisol was also evaluated as a measure of systemic bioactivity.. Ten asthmatic subjects, mean (s.e.mean) age 29 (3) years, FEV1 89 (5) % predicted, were randomised in a double-blind crossover study to receive inhaled placebo (PL), inhaled fluticasone 1000 microg day-1 (F1000) and inhaled fluticasone 2000 microg day-1, each for 4 days and also a single dose of oral prednisolone 50 mg (PRED). Prednisolone was given as open medication. The last dose of study drug was taken at 22.00 h and subjects attended the laboratory at 08.00 h the following day.. beta2-AR density (Bmax; fmol/10[6] cells) was significantly increased after PRED compared with PL and inhaled fluticasone. Bmax (geometric mean) after each treatment were: PL 1.51, F1000 1.20, F2000 1.20 and PRED 2.14 (a 1.4 fold difference PRED vs PL; 95% CI 1.05 to 1.95; P < 0.001). There was significant (P < 0.001) suppression of plasma cortisol (nmol l-1) following F2000 and PRED compared with PL: 393.8, F1000 302.1, F2000 205.0 (95% CI F2000 vs PL 58.1 to 319.4) and PRED 87.0 (95% CI PRED vs PL 176.2 to 437.5). The estimated milligram equivalence ratio for adrenal suppression was calculated at 1:11 for fluticasone vs prednisolone.. Repeated dosing with high-dose inhaled fluticasone did not up-regulate lymphocyte beta2-AR as compared with a single dose of oral prednisolone, despite having significantly suppressed early morning plasma cortisol. This study confirms our previous finding of a dissociation in sensitivity between effects of inhaled corticosteroid on adrenal suppression and lymphocyte beta2-AR regulation, at least for doses up to 2 mg day-1 of fluticasone.

Topics: Administration, Inhalation; Administration, Oral; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Lymphocytes; Middle Aged; Prednisolone; Receptors, Adrenergic, beta-2; Up-Regulation

The aim of the study was to evaluate the facilitatory effects of inhaled corticosteroid on in vitro parameters of lymphocyte beta 2-adrenoceptor function in asthmatic patients. Serum cortisol level was also evaluated as a measure of systemic bioactivity. Ten (four female) asthmatic subjects were evaluated, mean (SEM) age was 28.6(2.0) years, and FEV1 was 79.9%(8.7) predicted. Single doses of inhaled placebo (PL), fluticasone propionate, 1,000 micrograms (F1000), fluticasone propionate, 2,000 micrograms(F2000), or oral prednisolone, 50 mg(PRED), were given at 10 PM the previous night and measurements were made 10 h later. Values for beta 2-receptor density (logBmax: fmol/10(6)cells) were significantly (p < 0.05) greater than PL with PRED but not with inhaled fluticasone (as means and 95% confidence interval [CI] for difference vs PL): PL, 0.27; F1000, 0.30; F2000, 0.32; and PRED, 0.48 (95% CI vs PL, 0.075 to 0.341). Maximal cyclic adenosine monophosphate (cAMP) responses to isoproterenol hydrochloride (isoprenaline (Emax; pmol/10(6)cells) mirrored those for Bmax: PL, 4.00; F1000, 4.68; F2000, 4.26; and PRED, 7.46 (95% CI vs PL, -0.01 to 6.91). Receptor affinity (Kd) was not significantly altered by any treatment. There was significant (p < 0.05) suppression of serum cortisol (nmol/L) with F2000 and PRED compared with PL: PL, 307.9; F1000, 323.2; F2000, 130.1 (95% CI vs PL, 69.76 to 285.8) and PRED, 51.8 (95% CI vs PL, 144.11 to 368.01). Thus, high-dose inhaled fluticasone propionate did not have any facilitatory effects on lymphocyte beta 2-adrenoceptor parameters as compared with oral prednisolone which upregulated beta 2-receptor density and increased cAMP response. In contrast, high-dose inhaled fluticasone (2,000 micrograms) significantly suppressed serum cortisol. In conclusion, there would appear to be a dissociation in systemic sensitivity between effects of inhaled corticosteroid on adrenal suppression and lymphocyte beta 2-adrenoceptor regulation.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Female; Fluticasone; Humans; Hydrocortisone; Lymphocytes; Male; Prednisolone; Receptors, Adrenergic, beta

This double-blind, randomized, parallel-group, placebo-controlled study investigated the efficacy and tolerability of fluticasone propionate aerosol (25, 50, or 100 mg bid for 12 weeks) administered as primary maintenance therapy to patients whose mild to moderate asthma was inadequately controlled by as-needed use of an inhaled beta-agonist.. At all clinic visits, fluticasone propionate compared with placebo was associated with significant (P<.05) improvement in pulmonary function indexed by forced expiratory volume in 1 second (FEV1) as well as fewer night awakenings and less use of rescue albuterol. Values for patient-measured morning peak expiratory flow rates (PEFR) were significantly (P<.05) higher and the use of rescue albuterol was significantly (P<.05) lower beginning 3 to 5 days after initiation of therapy in the groups treated with fluticasone propionate, compared with the placebo group. Maximal improvement in FEV1 was achieved during the second week of treatment and maintained throughout the course of therapy. Differences among the three fluticasone propionate dosing groups for these efficacy measures were not statistically significant. The incidence of adverse events was similar across groups.. These data indicate that fluticasone propionate aerosol is an effective and well-tolerated treatment for asthma and significantly improves pulmonary function within days of initiation of treatment in patients whose asthma is inadequately controlled with as-needed beta-agonists.

Topics: Adolescent; Adult; Aerosols; Androstadienes; Anti-Asthmatic Agents; Asthma; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Treatment Outcome

Inhaled corticosteroids (ICS) in dosages above 1,000 micrograms/d may influence parameters of bone metabolism. Fluticasone propionate (FP) is a new ICS with a higher clinical potency than beclomethasone dipropionate (BDP) combined with negligible oral bioavailability. The aim of this study was to evaluate the effects of FP and BDP in clinically equipotent dosages on indices of bone metabolism and morning cortisol. FP 750 micrograms/d and BDP 1,500 micrograms/d were compared in a randomized, double-blind, crossover study consisting of two 6-wk treatment periods, each preceded by a 3-wk single-blind placebo period. Twenty-one nonsmoking asthmatic completed the study. FP had the same effect on FEV1 and peak expiratory flow as the double dose of BDP. Both treatments did not change morning cortisol. BDP decreased both osteocalcin and procollagen type 1 carboxyterminal propeptide, indices of bone formation, significantly by 18.5 and 21.9%, respectively. In contrast, FP did not change any variable of bone formation. FP and BDP did not increase type 1 collagen carboxyterminal telopeptide and deoxypyridinoline crosslinks, both markers of bone resorption. In changes in parameters of bone metabolism indicate adverse effects on bone quality in the long term, FP may offer an advantage over BDP.

Topics: Administration, Topical; Adolescent; Adult; Amino Acids; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bone and Bones; Bone Resorption; Circadian Rhythm; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Middle Aged; Osteocalcin; Osteogenesis; Peak Expiratory Flow Rate; Peptide Fragments; Procollagen; Single-Blind Method

Fluticasone propionate is a potent inhaled corticosteroid that is effective in improving pulmonary function and symptoms in patients with asthma.. To evaluate the effects of fluticasone propionate on quality of life in patients with severe asthma requiring oral corticosteroids.. A total of 96 patients with severe asthma participated in a randomized, double-blind, placebo-controlled, parallel-group, oral steroid-sparing study. Patients received fluticasone propionate aerosol, 750 or 1000 micrograms bid, or placebo for 16 weeks; 91 of these patients continued in a 1-year open-label study, in which everyone initially received fluticasone propionate, 1000 micrograms bid. At regular intervals, patients completed the Medical Outcomes Study Short Form-36 (SF-36), a general health status questionnaire measuring eight dimensions of quality of life, plus one question on change in health from the previous year.. Compared with the US population, patients scored significantly lower at baseline for five of eight SF-36 dimensions (P < .01). After 16 weeks, patients receiving fluticasone propionate, 1000 micrograms, improved significantly (P < or = .02) in physical functioning, role-physical, general health, and change in health, compared with the placebo group. After 1 year of open-label treatment with fluticasone propionate, these improvements were maintained. SF-36 scores in the placebo group during the double-blind period either worsened or remained unchanged; however, when these patients were switched to fluticasone propionate during the open-label period, their SF-36 scores also improved. Forced expiratory volume in 1 second (FEV1) at the end of the double-blind period was positively correlated with mean quality of life scores on physical functioning, role-physical, vitality, social functioning, and change-in-health status.. Health-related quality of life improved in patients with severe asthma following 16 weeks of treatment with fluticasone propionate, 1000 micrograms bid. These improvements were maintained during subsequent fluticasone propionate treatment over a 1-year period.

Topics: Administration, Oral; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Double-Blind Method; Female; Fluticasone; Follow-Up Studies; Humans; Male; Middle Aged; Quality of Life

Fluticasone propionate (FP) administered via metered-dose inhaler is a potent corticosteroid effective in the treatment of asthma. To evaluate the efficacy and safety of FP powder administered via a breath-activated inhaler (Diskhaler), a multicenter, double-blind, randomized, placebo-controlled, parallel-group study was conducted in adolescent and adult patients (n = 331) with mild-to-moderate asthma previously treated with beta 2-agonist therapy alone. Patients received FP powder 50, 100, or 250 micrograms or placebo twice daily for 12 weeks. FP-treated patients compared with placebo-treated patients had significantly (p < 0.001) greater improvements in morning predose forced expiratory volume in 1 sec (21-22% increase vs. 9%). Improvement in morning peak flow rate were also significantly (p < 0.001) greater with FP than with placebo (8-10% increase vs. 2% increase). There was also a significant overall treatment difference in the frequency of inhaled albuterol use (p < 0.001) and number of nighttime awakenings due to asthma (p = 0.005). There were no statistically significant difference among the FP treatment groups in any outcome measure. Physicians' global assessments also indicated significant (p < 0.001) differences in efficacy, with 67-74% of FP-treated patients rated as having "effective" or "very effective" treatment compared with 41% of placebo-treated patients. Significant beneficial effects of FP were observed in lung function and diary card parameters after just 1 week of treatment. Adverse events were similar across treatment groups and primarily related to local irritation. Effect on hypothalamic-pituitary-adrenal axis function was minimal. In summary, all three dosages of inhaled FP powder were well tolerated and improved various asthma-related variables. Improvements in pulmonary function, beyond those achieved with beta 2-agonist therapy alone, were maintained for the duration of the 12-week study.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Powders; Vital Capacity

The inhaled corticosteroid, fluticasone propionate, was compared with the oral bronchodilator theophylline in the maintenance treatment of asthma.. The objective of the present study was to compare the efficacy and safety of twice-daily inhaled fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, with that of theophylline in the maintenance treatment of mild-to-moderate asthma.. In this randomized, double-blind, placebo-controlled, parallel-group study, 353 adult and adolescent patients with asthma inadequately controlled with inhaled beta-agonist therapy alone received fluticasone propionate, 50 micrograms, or fluticasone propionate, 100 micrograms, by metered-dose inhaler; theophylline capsules; or placebo twice daily for 12 weeks. Only inhaled albuterol was permitted as needed for acute symptoms.. Both fluticasone propionate groups had a significantly greater probability of remaining in the study (ie, meeting asthma stability criteria) than did either the theophylline or placebo group (P < or = .008); 39% and 51% in the theophylline and placebo groups, respectively, were withdrawn due to lack of treatment efficacy compared with 14% and 21% in the fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, groups. Both fluticasone propionate groups experienced significantly greater improvement in FEV1 and PEF compared with patients in the theophylline or placebo group (P < or = .004). The incidence of potentially drug-related adverse events was significantly greater in the theophylline group (25%) than in the placebo group (11%) (P = .031), while there were no differences between placebo and fluticasone propionate, 50 micrograms, (18%) or fluticasone propionate 100 micrograms, (22%).. Twice daily treatment with inhaled fluticasone propionate 50 micrograms or 100 micrograms was significantly more effective than theophylline in the treatment of mild-to-moderate asthma.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Circadian Rhythm; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Multicenter Studies as Topic; Theophylline; Treatment Outcome

A study was performed to compare the adrenal suppression caused by inhaled fluticasone propionate and budesonide on a microgram equivalent basis, each given by metered dose inhaler to asthmatic patients.. Twelve asthmatic patients of mean age 29.9 years, with a forced expiratory volume in one second (FEV1) 92.9% predicted and forced expiratory flow 25-75% (FEF25-75) 69.5% predicted, on less than or equal to 400 micrograms/day inhaled corticosteroid, were studied in a double blind placebo controlled crossover design comparing single doses of inhaled budesonide 400, 1000, 1600, 2000 micrograms and fluticasone propionate 500, 1000, 1500, 2000 micrograms. Doses were administered at 22.00 hours by metered dose inhaler with mouth rinsing and measurements were made in the laboratory 10 hours later.. Serum cortisol levels compared with placebo (mean 325.2 nmol/l) were suppressed by fluticasone at doses of 1500 micrograms (211.6 nmol/l) and 2000 micrograms (112.3 nmol/l) and by budesonide at 2000 micrograms (243.4 nmol/l). Fluticasone propionate 2000 micrograms produced lower absolute serum cortisol levels than budesonide 2000 micrograms (95% CI for difference 42.9 to 219.2). The dose ratio (geometric mean) for the relative potency was 2.89 fold (95% CI 1.19 to 7.07). In terms of percentage suppression versus placebo, fluticasone propionate also produced greater effects (means and 95% CI for difference): budesonide 1600 micrograms (16.0) versus fluticasone propionate 1500 micrograms (40.9) (95% CI -0.6 to 50.6), budesonide 2000 micrograms (26.0) versus fluticasone 2000 micrograms (65.2) (95% CI 10.5 to 67.8). Individual serum cortisol levels at the two highest doses showed 15 of 24 patients below the normal limit of the reference range (150 nmol/l) for fluticasone and five of 24 for budesonide. Fluticasone propionate also caused greater ACTH suppression than budesonide (as % versus placebo): budesonide 1600 micrograms (12.0) versus fluticasone propionate 1500 micrograms (31.9) (95% CI 7.6 to 32.1), budesonide 2000 micrograms (13.5) versus fluticasone propionate 2000 micrograms (44.4) (95% CI 13.2 to 48.7). For overnight 10 hour urinary cortisol (nmol/10 hours) there was a difference between the lowest doses of the two drugs: budesonide 400 micrograms (37.2) versus fluticasone propionate 500 micrograms (19.9) (95% CI 6.9 to 27.8).. Like budesonide the systemic bioactivity of fluticasone propionate is mainly due to lung vascular absorption. Fluticasone propionate exhibited at least twofold greater adrenal suppression than budesonide on a microgram equivalent basis in asthmatic patients.

Topics: Administration, Topical; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Aerosols; Analysis of Variance; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Male; Pregnenediones

Topics: Administration, Topical; Adrenal Glands; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bone and Bones; Budesonide; Child; Cross-Over Studies; Double-Blind Method; Fluticasone; Glucocorticoids; Humans; Osteocalcin; Pregnenediones

Inhaled corticosteroids are considered to be effective and safe to treat children with asthma. These drugs, often used as maintenance treatment, can, however, influence the HPA-axis, which might be reflected by the serum and urine cortisol concentration. The aim of the present study was to investigate the efficacy and safety of fluticasone propionate (FP) 100 microg administered twice a day via a Diskhaler for 3 mo. FP was tested in a double-blind randomized placebo-controlled parallel trial in a group of 34 children with moderate asthma who did not use inhaled steroids for at least 4 wk prior to the study. At home, symptoms and peak flow recordings (PEFR) were noted in a diary. At each visit lung function was measured, and serum and urinary cortisol were determined. During treatment, wheezing decreased and PEFR values increased in the FP group. FEV1 and PC20-histamine increased and the reversibility decreased in the FP group. All changes were significant, with the exception of the change in nocturnal PEFR. Four weeks after cessation of FP all parameters returned to pretreatment values. Serum cortisol did not change significantly in either treatment group. The decrease in urinary cortisol in the FP group was significant only if it was compared with the increase in urinary cortisol in the placebo group. We conclude that FP 100 microg given twice a day is effective in children with moderate stable asthma. Suppression of the HPA-axis by FP 100 microg given twice daily, although not likely, cannot be ruled out by this study since the absence of a significant decrease in urinary cortisol in the FP group could be due to an insufficient number of patients. Additional studies are required to solve this problem.

Topics: Administration, Inhalation; Aerosols; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Peak Expiratory Flow Rate; Pituitary-Adrenal System; Respiratory Function Tests

Methacholine is frequently used to determine bronchial hyperresponsiveness (BHR) and to generate dose-response curves. These curves are characterized by a threshold (provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) = sensitivity), slope (reactivity) and maximal response (plateau). We investigated the efficacy of 12 weeks of treatment with 1,000 microg fluticasone propionate in a double-blind, placebo-controlled study in 33 atopic asthmatics. The outcome measures used were the influence on BHR and the different indices of the methacholine dose-response (MDR) curve. After 2 weeks run-in, baseline lung function data were obtained and a MDR curve was measured with doubling concentrations of the methacholine from 0.03 to 256 mg x mL(-1). MDR curves were repeated after 6 and 12 weeks. A recently developed, sigmoid cumulative Gaussian distribution function was fitted to the data. Although sensitivity was obtained by linear interpolation of two successive log2 concentrations, reactivity, plateau and the effective concentration at 50% of the plateau value (EC50) were obtained as best fit parameters. In the fluticasone group, significant changes occurred after 6 weeks with respect to means of PC20 (an increase of 3.4 doubling doses), plateau value fall in forced expiratory volume in one second (FEV1) (from 58% at randomization to 41% at 6 weeks) and baseline FEV1 (from 3.46 to 3.75 L) in contrast to the placebo group. Stabilization occurred after 12 weeks. Changes for reactivity were less marked, whereas changes in log, EC50 were not significantly different between the groups. We conclude that fluticasone is very effective in decreasing the maximal airway narrowing response and in increasing PC20. However, it is likely that part of this increase is related to the decrease of the plateau of maximal response.

Topics: Administration, Topical; Adolescent; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Methacholine Chloride; Middle Aged

The aim of this study was to compare fluticasone propionate (FP) with budesonide (BUD) at a dose of 400 microg x day(-1) in the treatment of children with asthma. Two hundred and twenty nine children with mild-to-moderate asthma, currently receiving 200-400 microg x day(-1) of inhaled corticosteroid, were randomized to receive either 400 microg x day(-1) of FP from the Diskhaler (registered trade mark of the Glaxo Group of Companies) or 400 microg x day(-1) of BUD from the Turbuhaler (registered trade mark of Astra Pharmaceuticals Ltd) for 8 weeks, in a parallel-group, double-blind, double-dummy study. Primary efficacy was assessed by measurement of daily peak expiratory flow (PEF). In addition, pulmonary function tests were performed at each clinic visit and a self-administered patient-centred questionnaire was completed by one parent of each patient at the start and end of study treatment. Mean morning PEF increased following treatment both with FP and BUD, but was significantly higher following treatment with FP during Weeks 1-4 (p=0.015) and Weeks 1-8 (p=0.019). Similar results were found for mean evening PEF and percentage predicted morning and evening PEF. Children receiving FP experienced significantly less disruption in their physical activities (i.e. sports, games) because of their asthma compared to children treated with BUD (p=0.03). Mean cortisol levels increased in both groups, but the increase was significantly higher in the FP group at 4 weeks (p=0.022). Serum and urine markers of bone formation and resorption changed very little and showed no consistent pattern of change. Fluticasone propionate at a dosage of 400 microg x day(-1) from the Diskhaler provided a more rapid and greater improvement in lung function in children with mild-to-moderate asthma than BUD 400 microg day(-1) from the Turbuhaler. Both treatments were well-tolerated, with a similar safety profile.

Topics: Administration, Topical; Adolescent; Aerosols; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bone and Bones; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Hydroxyproline; Male; Nebulizers and Vaporizers; Osteocalcin; Patient Satisfaction; Peak Expiratory Flow Rate; Peptide Fragments; Pregnenediones; Procollagen; Surveys and Questionnaires

Oral corticosteroids used in short courses for acute asthma are regarded as safe, although the frequent use of these drugs may result in patients suffering from systemic side effects. It has become common practice for patients to increase their own inhaled corticosteroid intake when their asthma goes out of control, but it has never been established whether a high dose of inhaled corticosteroid can be as effective as a short course of oral corticosteroid in the treatment of acute exacerbations.. A multicentre, randomised, double blind, double dummy, parallel group study was undertaken to determine whether the introduction of a high dose of inhaled fluticasone propionate (2 mg daily) is as effective as a short reducing course of oral prednisolone (starting at 40 mg/day and reducing by 5 mg every other day) in the treatment of acute exacerbations of asthma not considered severe enough for admission to hospital but requiring treatment with oral corticosteroid.. Four hundred and thirteen adult asthmatic subjects who presented to their general practitioner with an acute exacerbation of asthma were recruited in 47 general practices in the United Kingdom. Treatment failures, defined as a reduction in peak expiratory flow (PEF) to below 60% of the patient's best/predicted value on two consecutive occasions or persistent symptoms with no improvement on three consecutive days, occurred in 23% of patients who received oral prednisolone and 27% who received inhaled fluticasone propionate (difference in percentage of treatment failures 4.3, 95% CI -4.1 to 12.8, p = 0.31). In each group 48% were classified as treatment successes, defined as a 10% or greater increase in percentage best/predicted morning PEF. Both treatments were equally well tolerated.. There is no evidence of a significant difference in efficacy between a reducing dose course of oral prednisolone and high dose inhaled fluticasone propionate in mild exacerbations of asthma which do not require admission to hospital.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Prednisolone; Primary Health Care; Treatment Outcome

This study was designed primarily to assess the safety and tolerability of fluticasone propionate (FP) 1 mg day-1 by comparison with beclomethasone dipropionate (BDP) 2 mg day-1 over a 12-month study period. Lung function data were also recorded and used to determine whether the potency ratio between the two inhaled corticosteroids observed in previous studies was maintained in the long-term. Two hundred and thirteen patients with an established clinical history of severe chronic asthma and who were currently receiving between 1000 micrograms and 2000 micrograms day-1 of inhaled steroids were randomized to treatment in a ratio of 3:1 for FP:BDP (159 patients FP; 54 patients BDP), both via metered dose inhalers. Both treatments were well tolerated with a similar adverse event profile. No unexpected adverse events were recorded. Most adverse events were related to the patients' asthma, an intercurrent infection or underlying atopy. The incidence of pharmacologically predictable adverse events was equally low in both treatment groups as was the incidence of events suggestive of systemic steroid effect. Mean serum cortisol levels remained within the normal range at all visits for both treatments. At 12 months, however, the mean cortisol levels for the FP group had risen 4% above the baseline value but had dropped 15% below for the BDP group, giving a ratio of FP:BDP of 1.22; P = 0.01; 95% confidence limits (CL) 1.05-1.43. Fluticasone propionate 1 mg day-1 was at least as effective as BDP 2 mg day-1 in improving lung function (PEF, FEV1 and FVC) over this period. Moreover, the difference in FEV1 values at 6 months was significantly greater for the FP group than for the BDP group (P = 0.04; difference = 0.12 1; 95% CL = 0.01, 0.24 1). The difference between treatments in the amount of FEV1 reversibility was also significantly greater for FP at 12 months (difference in treatments = -3%; 95% CL = - 7-0%; P = 0.044). This study supports previous studies and suggests that FP is likely to be of benefit in the long-term treatment of chronic severe asthma.

Topics: Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Lung; Male; Middle Aged; Nebulizers and Vaporizers

The aim of this study was to compare the systemic bioactivity of inhaled budesonide (B) and fluticasone propionate (F), each given by large volume spacer, on a microgram equivalent basis in asthmatic children.. Ten stable asthmatic children of mean age 11 years and forced expiratory volume in one second (FEV1) 81.6% predicted, who were receiving treatment with < or = 400 micrograms/day of inhaled corticosteroid, were studied in a placebo controlled single blind (investigator blind) randomised crossover design comparing single doses of inhaled budesonide and fluticasone propionate 400 micrograms, 800 micrograms, and 1250 micrograms. Doses were given at 20.00 hours with mouth rinsing and an overnight 12 hour urine sample was collected for estimation of free cortisol and creatinine excretion.. The results of overnight 12 hour urinary cortisol output (nmol/12 hours) showed suppression with all doses of fluticasone propionate (as geometric means): F400 micrograms (11.99), F800 micrograms (6.49), F1250 micrograms (7.00) compared with placebo (24.43), whereas budesonide caused no suppression at any dose. A comparison of the drugs showed that there were differences at 800 micrograms and 1250 micrograms levels for urinary cortisol: B800 micrograms versus F800 micrograms (2.65-fold, 95% CI 1.26 to 5.58), B1250 micrograms versus F1250 micrograms (2.94-fold, 95% CI 1.67 to 5.15). The results for the cortisol/creatinine ratio were similar to that of urinary cortisol, with fluticasone causing suppression at all doses and with differences between the drugs at 800 micrograms and 1250 micrograms.. Single doses of inhaled fluticasone produce greater systemic bioactivity than budesonide when given by large volume spacer on a microgram equivalent basis in asthmatic children. The systemic bioactivity of fluticasone, like budesonide, is due mainly to lung bioavailability.

Topics: Administration, Inhalation; Adolescent; Adrenal Glands; Analysis of Variance; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Creatinine; Cross-Over Studies; Female; Fluticasone; Humans; Hydrocortisone; Male; Pregnenediones; Single-Blind Method

An economic analysis was conducted comparing the cost effectiveness of fluticasone propionate with that of sodium cromoglycate (cromolyn sodium) in a group of children aged 4 to 12 years old with asthma, who required inhaled prophylactic therapy. Over an 8-week study period, 115 patients received sodium cromoglycate 20mg 4 times daily, via the spin operated dry powder inhaler, and 110 patients received fluticasone propionate 50 micrograms twice daily, via the Diskhaler (trademark held by the Glaxo Wellcome Group of Companies). Patient healthcare resource use was examined in terms of study medication, the use of rescue medication [salbutamol (albuterol) 200 micrograms] and the number of hospitalisations. The effectiveness of both treatments was examined over a range of success and failure criteria embracing peak expiratory flow rate (PEFR) improvement, symptom control and the level of adverse events related to the study medication. Results indicate that, for each UK pound spent, fluticasone propionate was associated with twice as many successfully treated patients as sodium cromoglycate, using a range of outcomes based on the goals of treatment defined in the British Thoracic Society's asthma guidelines. It is concluded that fluticasone propionate was more cost effective than sodium cromoglycate in improving PEFR and symptom control in this group of children with asthma who had a clinical requirement for prophylactic therapy.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Cost-Benefit Analysis; Cromolyn Sodium; Fluticasone; Humans; Peak Expiratory Flow Rate; United Kingdom

Fluticasone propionate is a new inhaled corticosteroid with a 2:1 efficacy ratio compared with beclomethasone dipropionate with regard to lung function and symptom scores, without increased systemic activity. The aim of this study was to investigate whether this was also the case for bronchial hyperresponsiveness, assessed by both a direct (histamine) and an indirect (ultrasonically nebulised distilled water (UNDW)) provocation test.. Fluticasone propionate, 750 micrograms/day, and beclomethasone dipropionate, 1500 micrograms/day, were compared in a randomised, double blind, crossover study consisting of two six week treatment periods, each preceded by a three week single blind placebo period. Twenty one non-smoking asthmatics (mean forced expiratory volume in one second (FEV1) 74.7% predicted, mean PC20histamine 0.36 mg/ml) completed the study.. Fluticasone propionate and beclomethasone dipropionate improved FEV1, peak flow rates, asthma symptoms, and bronchial hyperresponsiveness to the same extent. Both fluticasone propionate and beclomethasone dipropionate caused an increase in PC20histamine (mean 2.29 [95% confidence interval 1.45 to 3.13] and 1.95 [1.07 to 2.84] doubling doses, respectively) and in PD20UNDW (1.12 [0.55 to 1.70] and 1.28 [0.88 to 1.70] doubling doses, respectively). Neither treatment changed morning serum cortisol levels, but fluticasone propionate decreased the number of peripheral blood eosinophils less than beclomethasone dipropionate, indicating smaller systemic effects of fluticasone propionate.. These findings show that fluticasone propionate is as effective as twice the dose of beclomethasone dipropionate on bronchial hyperresponsiveness, assessed by provocation with both histamine and UNDW, without increased systemic activity.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchial Hyperreactivity; Bronchial Provocation Tests; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Peak Expiratory Flow Rate

This study examined the ability of fluticasone propionate aerosol to reduce oral prednisone requirements in patients with severe asthma. Ninety-six patients dependent on oral prednisone were treated for 16 wk with placebo or fluticasone propionate aerosol (750 or 1,000 micrograms twice daily). Their dosage of oral prednisone was adjusted weekly according to predetermined criteria. A total of 69% and 88% of patients treated with fluticasone propionate 750 and 1,000 micrograms twice daily, respectively, compared with 3% of placebo-treated patients used no prednisone by the end of the study. In the fluticasone propionate groups, FEV1 and peak expiratory flow rates at the last evaluable visit/date improved and the number of night awakenings and symptomatic albuterol use declined relative to placebo values (p < 0.05). Patient-rated asthma symptoms improved in the groups receiving fluticasone propionate but not in the placebo group (p < 0.005). Fluticasone propionate aerosol was well-tolerated, and it improved some dimensions of health-related quality of life measured using a standard patient survey. Fluticasone propionate aerosol (750 or 1,000 micrograms twice daily) effectively and safely allowed most asthmatics dependent on oral corticosteroids to reduce or eliminate oral prednisone use while improving pulmonary function and quality of life.

Topics: Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aerosols; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Prednisone; Quality of Life

Inhaled corticosteroids are highly effective in the treatment of asthma at all ages and their use in younger children is increasing. As concerns exist about the long-term systemic side-effects of high dose inhaled corticosteroids, current guidelines continue to recommend sodium cromoglycate (SCG) as first line regular medication for children with frequent symptoms. Few published studies have compared the safety and efficacy of inhaled corticosteroids with SCG in children. This study compares SCG with the new inhaled corticosteroid, fluticasone propionate (FP), which has theoretical advantages over other currently available corticosteroids due to its negligible oral bioavailability. This was a randomized, open, multi-centre, parallel group comparison of 50 micrograms FP twice daily and 20 mg SCG four times daily over 8 weeks, preceded by a 2-week baseline period. Sixty-two general practices and two hospital centres enrolled 225 asthmatic children aged 4-12 years (110 received FP; 115 received SCG). Outcome measures improved in both groups, with a significant difference in favour of FP for the key variables of mean morning and evening % predicted PEFR and % of symptom-free days and nights. No significant difference was observed for FEV1, or relief medication use. Two children taking FP and 10 children taking SCG withdrew because of adverse events. This study showed that low dose FP was effective and superior to SCG in young children with mild-moderate asthma. Safety studies of longer duration are needed before changing the current recommendations for inhaled corticosteroid therapy.

Topics: Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Child, Preschool; Cromolyn Sodium; Female; Fluticasone; Humans; Male; Multivariate Analysis; Peak Expiratory Flow Rate

Airway inflammation is now regarded as fundamental in the pathogenesis of asthma and treatment with inhaled corticosteroids has proved effective. There is a need for drugs in this category with higher topical potency but fewer side-effects than those presently available. A double-blind, parallel group study was conducted in 671 patients with severe asthma (already taking between 0.8-2.0 mg of inhaled corticosteroid daily) to compare the safety and efficacy of 6 weeks of treatment with inhaled fluticasone propionate (FP), 1 mg daily, to fluticasone propionate, 2 mg daily, and budesonide (BUD), 1.6 mg daily, delivered via a metered-dose inhaler. Peak expiratory flow (PEF), asthma symptoms, and usage of rescue medication were recorded daily by the patient. At each clinic visit (-2, 0, 3 and 6 weeks) morning serum cortisol levels, bone markers and spirometry were assessed. The changes in mean morning PEF from baseline (weeks 1-6) were: FP 2 mg daily +24 l.min-1; FP 1 mg daily +21 l.min-1; BUD 1.6 mg daily +13 l.min-1. A similar rank order for the three treatments was seen for evening PEF, clinic spirometry, reduction of diurnal PEF variation, symptom scores, and requirement for rescue bronchodilators. The mean serum cortisol levels remained well within the normal range in all three groups. Analysis of the geometric mean cortisol ratio (treatment/baseline ratio after 6 weeks treatment) showed a changed rank order, the values being: FP 1 mg daily 1.04; BUD 1.6 mg daily 0.97; FP 2 mg daily 0.88.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aerosols; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Budesonide; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Pregnenediones; Respiratory Function Tests; Time Factors

Current metered dose inhalers (MDIs) contain chlorofluorocarbon (CFC) propellants. A new propellant HFA134a, with no effect on ozone, may be a suitable alternative. Four asthma medications, salbutamol, salmeterol, fluticasone propionate (FP) and beclomethasone dipropionate (BDP), currently containing standard CFC propellants, were formulated with HFA134a for investigation. Single doses of salbutamol (200 micrograms) and salmeterol (50 micrograms, 100 micrograms) provided equivalent protection against bronchial provocation, after histamine and methacholine respectively, compared with the current preparation. A double-blind 4 week study comparing the two formulations of salbutamol, used as required in mild to moderate asthma, showed similar effects on morning peak expiratory flow rates (PEFR) and inhaler use. Salmeterol (50 micrograms) twice daily was compared with the current formulation in a 4 week trial. Improvement in morning PEFR was similar for both formulations. A double-blind study compared the two formulations of FP (250 micrograms) twice daily in moderate asthmatics previously taking 400-1,000 micrograms of inhaled corticosteroid daily. Morning PEFR improved in both groups. Safety and tolerability of the HFA134a product were similar to current formulations. The HFA134a formulations of salbutamol, salmeterol and FP provide equivalent efficacy with a similar safety profile to the existing formulations at equivalent doses.

Topics: Adult; Aerosol Propellants; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Child; Cross-Over Studies; Double-Blind Method; Fluticasone; Humans; Hydrocarbons, Fluorinated; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Salmeterol Xinafoate; Technology, Pharmaceutical

We wanted to evaluate the improvement in efficacy when increasing the daily dose of inhaled steroids and to compare the efficacy, safety, and tolerance of 1.6 mg beclomethasone dipropionate (BDP) with that of 2.0 mg fluticasone propionate (FP). The study was a randomized, double-blind, 3 month, multicentre study. One hundred and thirty four asthmatics currently using inhaled steroids (0.4-1.6 mg BDP or budesonide (BUD)) were stratified according to pretrial daily steroid use. Within each stratum they were randomized to either 1.6 mg BDP or 2.0 mg FP. A significant increase in the primary efficacy variables, i.e. mean morning and evening peak expiratory flow (PEF) (approximately 20 l.min-1) during the treatment period, was found for both treatments. No significant differences between the drugs were revealed for these primary or any other secondary efficacy variables (use of beta 2-agonists, symptom scores, and PEF, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) recorded at the clinical visits). However, significant differences between treatments occurred regarding decrease of serum cortisol and adrenocorticotropic hormone. We conclude that, although both treatments gave statistically significant increases in efficacy parameters when compared with baseline, the increases were so small that they can be regarded as being clinically unimportant. Daily doses of BDP, 1.6 mg, and FP, 2.0 mg, had comparable effects on lung function. A suppression of the hypothalamic pituitary adrenal (HPA) axis was only found with a daily dose of 2 mg FP.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Depression, Chemical; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Peak Expiratory Flow Rate; Pituitary-Adrenal System; Vital Capacity

Recent emphasis on the control of airway inflammation in asthma highlights the need for safe and effective antiinflammatory agents. Fluticasone propionate is one of the most potent antiinflammatory corticosteroids developed to date.. This study assessed the safety and efficacy of fluticasone propionate aerosol in the treatment of mild to moderate asthma.. Fluticasone propionate aerosol (25, 100, or 500 micrograms twice daily) or placebo was given for as long as 8 weeks to adults with mild to moderate asthma in a randomized, double-blind, parallel-group study. Patients were removed from the study if they showed predefined signs of worsening asthma.. Sixty-three percent of placebo-treated patients and 23%, 13%, and 4% of patients treated with fluticasone propionate 25, 100, and 500 micrograms twice daily, respectively, were removed from the study. Mean forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow at midexpiratory phase at weekly visits throughout the study demonstrated that fluticasone propionate was more efficacious than placebo in maintaining asthma control. Measurements of peak expiratory flow and symptom scores significantly improved and nighttime awakenings and albuterol use to treat symptoms significantly declined in fluticasone propionate-treated groups relative to the placebo-treated group. Differences among fluticasone propionate groups for these variables were not statistically significant. Incidence and severity of adverse events were similar across groups. Fluticasone propionate did not affect morning or stimulated plasma cortisol concentrations, although slight, transient reductions in urinary free cortisol and urinary 17-hydroxy steroids occurred in the group receiving 500 micrograms fluticasone propionate twice daily.. These data indicate that fluticasone propionate provides safe and effective treatment for mild to moderate asthma.

Topics: Administration, Topical; Adult; Aerosols; Androstadienes; Anti-Inflammatory Agents; Asthma; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Male; Patients; Physicians; Pituitary-Adrenal System; Spirometry; Treatment Outcome

A total of 261 patients with symptomatic, mild to moderate asthma were randomized to treatment in this 4-week, double-blind, parallel-group comparison of fluticasone propionate 200 micrograms/d with beclomethasone dipropionate 400 micrograms/d. Improvements from both treatments were seen in diary card data. Morning peak expiratory flow rate (PEFR) improved from 375 to 390 and 371 to 382 l/min with fluticasone propionate and beclomethasone dipropionate, respectively. Symptom scores, percentage of symptom-free days and nights, and use of rescue beta 2-agonist medication also improved, as did clinical lung function. With the exception of percentage of rescue-free days, which was greater for beclomethasone dipropionate, none of the differences between the groups were statistically significant. There was a significant difference between treatments in the number of rescue-free days over days 1-28; however, there was no difference between treatments in the number of rescue-free days over days 1-14, nor was there any difference in the number of inhalations of rescue medication used throughout the study. Very few adverse effects were reported. Although all mean plasma cortisol values were within the normal range, they were significantly different between treatments, rising from 402 to 429 nmol/l with fluticasone propionate, and falling from 435 to 394 nmol/l with beclomethasone dipropionate (P = 0.006). Mean stimulated cortisol levels 30 min after tetracosactin injection were also significantly greater with fluticasone propionate (P = 0.024). In conclusion, fluticasone propionate 200 micrograms/d is as effective as beclomethasone dipropionate 400 micrograms/d with less effect on plasma cortisol levels.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Cosyntropin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Injections; Male; Middle Aged; Peak Expiratory Flow Rate; Time Factors; Treatment Outcome

High dose inhaled glucocorticosteroids are increasingly used in the management of patients with moderate to severe asthma. Although effective, they may cause systemic side effects. Fluticasone propionate is a topically active inhaled glucocorticosteroid which has few systemic effects at high doses.. Fluticasone propionate, 1.5 mg per day, was compared with beclomethasone dipropionate at the same dose for one year in patients with symptomatic moderate to severe asthma; 142 patients received fluticasone propionate and 132 received beclomethasone dipropionate. The study was multicentre, double blind and of a parallel design. For the first three months patients attended the clinic every four weeks and completed daily diary cards. For the next nine months they were only seen at three monthly intervals in the clinic.. During the first three months diary card peak expiratory flow (PEF) rate and lung function measurements in the clinic showed significantly greater improvement in patients receiving fluticasone propionate (difference in morning PEF 15 l/min (95% CI 6 to 25)), and these differences were apparent at the end of the first week. The improved lung function was maintained throughout the 12 month period and the number of severe exacerbations in patients receiving fluticasone propionate was reduced by 8% compared with those receiving beclomethasone dipropionate. No significant differences between the two groups were observed in morning plasma cortisol levels, urinary free cortisol levels, or response to synthetic ACTH stimulation. In addition, both the rates of withdrawal and of adverse events were low, and there were fewer exacerbations of asthma with fluticasone propionate than beclomethasone dipropionate.. This study shows that fluticasone propionate in a daily dose of 1.5 mg results in a significantly greater increase in PEF and asthma control than the same dose of beclomethasone dipropionate, with no increase in systemic or other side effects.

Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Double-Blind Method; Female; Fluticasone; Humans; Hydrocortisone; Lung; Male; Middle Aged; Peak Expiratory Flow Rate

This study was designed to compare the efficacy and safety of a new inhaled corticosteroid, fluticasone propionate at a total daily dose of 200 micrograms, with beclomethasone dipropionate 400 micrograms/day in childhood asthma. A total of 398 asthmatic children (aged 4-19 years) were randomised to receive either fluticasone propionate 200 micrograms daily or beclomethasone dipropionate 400 micrograms daily for six weeks inhaled via a spacer device from a metered dose inhaler. During the study the patients recorded morning and evening peak expiratory flow rate (PEFR), symptom scores, and use of beta 2 agonist rescue medication. In addition, clinic visit PEFR and forced expiratory volume in one second were measured. Safety was assessed by recording all adverse events and by performing routine biochemistry and haematology screens including plasma cortisol concentration before and after treatment. For the purposes of analysis the diary card data were grouped into three periods: week 3 (days 15-21), week 6 (days 36-42), and weeks 1-6 (days 1-42). The results showed no significant difference between treatments on most efficacy parameters. However, there were significant differences in changes from baseline in favour of fluticasone propionate for % predicted morning PEFR both at week 3 (fluticasone propionate 6.1%, beclomethasone dipropionate 3.9%) and at week 6 (fluticasone propionate 8.3%, beclomethasone dipropionate 5. 9%) and % predicted evening PEFR at week 6 (fluticasone propionate 7.3%, beclomethasone dipropionate 4.9% and over weeks 1-6 (fluticasone propionate 5.5%, beclomethasone dipropionate 3.6%. Comparison between groups showed that the group receiving fluticasone propionate had a lower % of days with symptom-free exercise at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 81%) and % days without rescue medication at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 80%) and over weeks 1-6 (fluticasone propionate 80%, beclomethasone dipropionate 73%). Except for a higher incidence of sore throat in the fluticasone propionate group, the two treatments did not differ with regard to safety. There was no evidence of adrenal suppression with either treatment. In conclusion, fluticasone propionate 200 microgram daily ws at least as effective and as well tolerated as beclomethasone dipropionate 400 microgram daily in childhood asthma.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Child, Preschool; Double-Blind Method; Drug Administration Schedule; Drug Delivery Systems; Female; Fluticasone; Humans; Lung; Male; Nebulizers and Vaporizers; Peak Expiratory Flow Rate

In this 4-week, multicenter, double-blind, randomized, parallel group study, the dose-effect relationship of four doses of inhaled fluticasone propionate (50, 100, 200, and 400 micrograms twice daily) was investigated and compared with beclomethasone dipropionate, 200 micrograms twice daily. A total of 672 patients with moderate asthma currently receiving 1,000 micrograms/d or less of an inhaled steroid were recruited. The study demonstrated a significant dose-related improvement in lung function with fluticasone propionate. Linear dose-related increases were observed in morning (increase per doubling dose was 4.3 L/min; 95 percent confidence interval [CI], 1.8, 6.8 L/min; p = 0.001) and evening peak expiratory flow rate (PEFR) (increase per doubling dose was 3.0 L/min; 95 percent CI, 0.5, 5.5 L/min; p = 0.017), clinic lung function (at 4 weeks, increase in percent predicted PEFR per doubling dose = 1.1 percent; 95 percent CI, 0.2, 2.1 percent; p = 0.022; increase in percent predicted FEV1 per doubling dose = 1.1 percent; 95 percent CI, 0.3, 1.9 percent; p = 0.10:increase in percent predicted FVC per doubling dose = 1.3 percent, 95 percent CI, 0.5, 2.1 percent; p = 0.001), and the percentage of symptom-free days over days 1 to 14 of treatment (increase per doubling dose = 1.9, 95 percent CI, 0.0, 3.9; p = 0.048). There was also a dose-related reduction in extra bronchodilator usage (days 1 to 14 p = 0.002; days 15 to 28 p = 0.01). In addition, there was a significant decrease in diurnal variation with increasing doses of fluticasone propionate (decrease per doubling dose = 2.0 L/min, 95 percent CI, 0.4; p = 0.024). The number of asthma exacerbations was also reduced as the dose of fluticasone propionate increased. Fluticasone propionate was well tolerated, adverse events were few, and there was a similar incidence in all groups. Furthermore, there was no evidence of any hypothalamic pituitary adrenal axis suppression. The data from the study were consistent with other clinical studies that have shown fluticasone propionate to be more potent than beclomethasone dipropionate in terms of improvement in lung function. In conclusion, this study provided evidence of a dose-related improvement in asthma control for fluticasone propionate in the dose range 100 to 800 micrograms daily, in patients with moderate asthma.

Topics: Administration, Topical; Adolescent; Adult; Aged; Analysis of Variance; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Humans; Male; Middle Aged; Respiratory Function Tests

Fluticasone propionate is a synthetic steroid for use by the inhaled route. It's high topical potency and low systemic bioavailability make it suitable for use in asthmatic children. A total of 258 children were randomised in a double-blind study to receive fluticasone propionate (50 micrograms bd) as the dry powder formulation inhaled via a Diskhaler inhaler, or matched placebo (with current therapy) for 4 weeks throughout which time diary cards were completed. During clinic visits lung function and adrenal function were measured. Fluticasone propionate produced a significantly greater increase in morning peak expiratory flow rate (PEFR) (adjusted mean difference over days 1-28, 17 l/min (95% CI; 10, 24); P < 0.001) and evening PEFR (adjusted mean difference over days 1-28, 16 l/min (95% CI; 9, 23); P < 0.001). In addition, diary card symptom scores, beta 2-agonist rescue and clinic lung function improved significantly on fluticasone propionate. There were few adverse events and basal plasma cortisol remained within the normal range. In conclusion fluticasone propionate at 50 micrograms bd is superior to placebo (current therapy) in the treatment of childhood asthma with no evidence of adverse effects.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Androstadienes; Anti-Inflammatory Agents; Asthma; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Peak Expiratory Flow Rate

Five hundred and eighty-five patients with moderate asthma, currently receiving 400-1000 micrograms day-1 of an inhaled corticosteroid, were treated for 6 weeks in a double-blind, randomized, parallel group study with either 500 micrograms day-1 fluticasone propionate as a dry powder via a Diskhaler inhaler, 500 micrograms day-1 fluticasone propionate via a pressurized inhaler or 1000 micrograms day-1 beclomethasone dipropionate via a pressurized inhaler. For all three treatment groups, mean morning and evening peak expiratory flow rates (PEFRs) increased within 1 week of the start of treatment. There were also improvements in clinic lung function, daytime and night-time asthma symptoms and a reduction in daytime and night-time rescue bronchodilator medication in all three groups. There were no statistically significant differences between the two formulations of fluticasone propionate in any of the efficacy parameters. Fluticasone propionate via the Diskhaler was significantly more effective than beclomethasone dipropionate over the 6 week study period in reducing diurnal variation (mean difference--4 l min-1, 95% CI--8 to 0 l min-1: P = 0.03). Fluticasone propionate via the Diskhaler produced a statistically significant improvement in night-time symptoms when compared to beclomethasone dipropionate whereas, beclomethasone dipropionate 1000 micrograms day-1 was statistically significantly more effective than both formulations of fluticasone propionate in improving daytime symptoms (P < 0.05). However, these statistical differences must be viewed together with the fact that very few patients recorded a score of 2 or more for both daytime or night-time symptoms. There was a similarly low incidence of adverse events with all three treatments with no evidence of hypothalamic pituitary adrenal (HPA)-axis suppression. The results of the 6-week comparative study showed that 500 micrograms day-1 fluticasone propionate whether administered via pressurized inhaler or Diskhaler is as effective and as safe as 1000 micrograms day-1 beclomethasone dipropionate administered via a pressurized inhaler in the treatment of moderate asthma. Over 12 months fluticasone propionate 500 micrograms day-1 via a pressurized inhaler was at least as effective and as well tolerated as beclomethasone dipropionate 1000 micrograms day-1.

Topics: Adolescent; Adult; Aerosols; Aged; Aged, 80 and over; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Humans; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Powders

Short-term lower leg growth was investigated with twice weekly knemometry measurements in 19 schoolchildren with mild asthma during treatment with daily doses of 200 micrograms fluticasone propionate, 400 micrograms, and 800 micrograms beclomethasone dipropionate from a dry powder inhaler. The design was a randomised, double blind, crossover trial. After a run in period of four days (period 1) the children were allocated to a sequence of active treatments in periods 2, 4, and 6. In periods 3 and 5 (wash out) placebo was given. All periods except the run in were two weeks long. The mean lower leg growth velocities during the wash out periods were 0.61 and 0.80 mm/week. Mean growth velocities during treatment with fluticasone propionate and low and high doses of beclomethasone dipropionate were 0.34, 0.09, and 0.06 mm/week respectively. Compared with fluticasone propionate, treatment with beclomethasone dipropionate 400 and 800 micrograms/day was associated with a statistically significant reduction in growth velocity.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Glucocorticoids; Growth; Humans; Leg; Male; Risk Factors; Time Factors

In order to study the adverse reaction of a new, inhaled steroid (Fluticasone) on the pituitary-adrenocortical axis in asthmatic children, we investigated 7 children (aged 7 to 15 years) before and during treatment with Fluticason (100-200 micrograms/day). For the dosage tested, we found no depression of adrenal function, neither in circadian cortisol secretion nor in hCRH-stimulation-test. Another 7 asthmatic children under treatment with Budesonide (800 micrograms/day) were examined by the same tests. They equally did not show an adrenocortical suppression. However, in 4 other children under therapy with oral prednisone (2.5 to 7.5 mg/day), there was a marked suppression on adrenocortical function, even with low doses of the steroid. We conclude that Fluticasone (as well as Budesonide) in the above dosages represent a safe therapy for bronchial asthma in children.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenal Cortex; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Budesonide; Child; Corticotropin-Releasing Hormone; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocortisone; Male; Pituitary-Adrenal System; Prednisolone; Pregnenediones

We wanted to compare the efficacy and safety of fluticasone propionate, a new topically active inhaled corticosteroid, to that of high dose beclomethasone dipropionate, in severe adult asthma. Patients currently receiving between 1.5-2.0 mg.day-1 of an inhaled corticosteroid were treated for six weeks in a double-blind, randomized, parallel group study with 1 mg.day-1 fluticasone propionate (n = 82), or 2 mg.day-1 beclomethasone dipropionate (n = 72). Mean morning peak expiratory flow rates (PEFR) increased from 303 to 321 l.min-1 with fluticasone propionate, and from 294 to 319 l.min-1 with beclomethasone dipropionate. There was an increase in evening PEFR, asthma symptoms improved, and rescue beta 2-agonist use decreased for both treatment groups. None of these differences between treatments were statistically significant. However, diurnal variation was significantly reduced with fluticasone propionate, when compared with beclomethasone dipropionate (difference = 7 l.min-1; p = 0.038). Clinic lung function also improved with both treatments and, apart from % predicted PEFR, which showed no difference after beclomethasone dipropionate but increased from 73 to 78% with fluticasone propionate, there were no differences between treatments. Forced expiratory volume in one second (FEV1) increased with both treatments. The geometric mean plasma cortisol concentration rose after treatment with fluticasone propionate (from 293 to 309 nmol.l-1) and fell after beclomethasone dipropionate (from 256 to 224 nmol.l-1); the difference between treatments was significant. The incidence of adverse events was low in both treatment groups. In conclusion, 1 mg.day-1 fluticasone propionate was as effective as 2 mg.day-1 beclomethasone dipropionate in the control of severe asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Topical; Adolescent; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Vital Capacity

Allergen challenge is associated with an increased excretion of urinary leukotriene E4. The source of this increase is unknown, although the lack of effect of inhaled beta-agonists and sodium cromoglycate suggests that airway mast cells may not be involved. We investigated this further using a new and topically potent inhaled glucocorticoid, fluticasone propionate (FP). A group of 10 mild atopic asthmatic subjects (6 males; FEV1 > 60% of predicted; PC20 histamine < or = 8 mg/ml; and on inhaled beta 2-agonists only) were studied before and after a 2-wk period of FP (1,000 micrograms/day) or placebo administered by metered-dose inhalers as two puffs twice per day through a large-volume spacer. Treatments were assigned in a double-blind crossover fashion separated by a 3-wk washout period. The PC20 histamine was measured at the start and end of each treatment when subjects also received a bronchial allergen challenge. Urine was collected for 4 h after allergen challenge for determination of LTE4 using HPLC-RIA, and 2 h later the PC20 histamine measurement was repeated. The 2-wk treatment with FP significantly inhibited both early and late responses to allergen: the maximum % fall in FEV1 during the early (0 to 2 h) and late response (2 to 6 h) was 32.6 +/- 3.4 and 19.6 +/- 5.2, respectively, following placebo versus 19.5 +/- 4.5 and 3.6 +/- 2.6 following FP (both p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Administration, Topical; Adult; Allergens; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchial Provocation Tests; Bronchoconstriction; Female; Fluticasone; Forced Expiratory Volume; Glucocorticoids; Histamine; Humans; Leukotriene E4; Male; SRS-A; Time Factors

In recent years, the combination of fluticasone furoate and vilanterol (FF/VI) has emerged as an alternative therapy, since it is administered every 24 h, in contrast to other ICS/LABAs such as fluticasone propionate plus salmeterol (FP/Salm), which requires administration every 12 h. Concerns have arisen over whether the benefit generated by FF/VI justifies the additional costs it involves over FP/Salm. This study aimed at assessing the health and economic consequences of FF/VI in patients with moderate-severe persistent asthma.. A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with persistent asthma. Total costs and QALYs for FF/VI and FP/Salm were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000.. We estimated a gain of 16.8 and 10.7 QALYs per patient per year on FF/VI and FP/Salm, respectively. At the same time, we observed a difference of US$216 in total discounted cost per person-year on FF/VI with respect to FP/Salm. The incremental cost-effectiveness ratio (ICER) of FF/VI was USD $70 per QALY with respect to FP/Salm. In the deterministic and probabilistic sensitivity analyses, our base-case results were robust to variations in all assumptions and parameters.. FF/VI is more cost-effective than FP/Salm. The evidence supports using FF/VI therapy in Colombia, and the study should be replicated in other middle-income countries.

Topics: Administration, Inhalation; Androstadienes; Asthma; Benzyl Alcohols; Chlorobenzenes; Cost-Benefit Analysis; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Treatment Outcome

The effectiveness of a fix-dose salmeterol/fluticasone combination therapy in asthma was previously shown for the original product. The study aim was to evaluate the clinical effectiveness and safety of a second entry DPI - dry powder inhaler (Salflumix Easyhaler) in patients with asthma in everyday clinical practice.. This multicenter Investigator-Initiated Study that enrolled 2,037 adult outpatients with asthma treated with Salflumix Easyhaler, was conducted by 220 pulmonologists across Poland. Asthma control was assessed during 3 visits with 6 ± 2 weeks intervals based on the Asthma Control Test (ACT). In addition, patient Satisfaction with Asthma Treatment Questionnaire (SATQ) and adherence and adverse events (AEs) were monitored.. During the observation (86 ± 30 days) the percentage of patients with controlled asthma (ACT 20-25 pts) increased from 35.5% at the first visit to 86.5% at the third visit (. Salflumix Easyhaler is highly effective and well-tolerated by naïve patients with asthma and those switching from another device. In general, patients show good compliance with medical product and are satisfied with the use of this new device, and not reporting difficulties and errors related to its' use. Their physicians' overall perception of Salflumix Easyhaler use is very positive.

Topics: Adult; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Patient Satisfaction; Salmeterol Xinafoate; Treatment Outcome

Allergic asthma is associated with anxiety-related behaviors, leading to poor quality of life. Previous studies mainly described the neuropathophysiology of asthma-induced anxiety. However, the effects of corticosteroids, the most common anti-inflammatory agents for asthma treatment, on the neurophysiological foundations of allergic asthma-induced anxiety are unexplored.. Here, we evaluated lung and brain inflammation as well as anxiety in an animal model of allergic asthma pretreated with inhaled fluticasone propionate. Furthermore, to define the neurophysiological bases of these conditions, we studied the medial prefrontal cortex (mPFC)-amygdala circuit, which is previously shown to accompany asthma-induced anxiety.. Our data showed that allergen induces anxiety, mPFC and amygdala inflammation, as well as disruptions in the local and long-range oscillatory activities within the mPFC-amygdala circuit. Interestingly, we observed a roughly consistent trend of changes with inhaled fluticasone pretreatment. Namely, the asthma-induced behavioral, inflammatory, and neurophysiological changes were partly, but not totally, prevented by inhaled fluticasone pretreatment.. We suggest that early treatment of asthmatic patients with inhaled corticosteroids improves mPFC-amygdala circuit function by attenuating neuroinflammation leading to reduced anxiety. These findings could lead clinical guidelines of asthma to consider the neuropsychiatric disorders of patients in treatment recommendations.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Amygdala; Androstadienes; Animals; Anxiety; Asthma; Fluticasone; Prefrontal Cortex; Quality of Life

Asthma is often exacerbated by airway infection, and some patients with severe asthma may be unresponsive to conventional corticosteroid treatment. Src family kinases (SFKs) were recently implicated in the inflammatory responses of mice induced by allergen and bacterial toxin lipopolysaccharide (LPS). Therefore, we examined the effects of dasatinib (DAS), a Src inhibitor, on airway inflammation in mice induced by ovalbumin (OVA) and LPS. Male A/J mice were sensitized to OVA Day -14 and -7, challenged with intranasal OVA on Day 0, 2, 4, 6 and 8, and on Day 10, mice were also challenged with OVA via inhalation. Mice were treated intranasally with DAS or fluticasone propionate (FP), a glucocorticoid, twice daily for 3 d starting 1 d after OVA inhalation. Moreover, some mice were also administrated LPS 2 h after DAS or FP treatment to model of asthma exacerbation. One day after the last intervention, lung tissue and bronchoalveolar lavage fluid (BALF) were collected. DAS attenuated the accumulation of inflammatory cells and cytokines/chemokines in BALF induced by both OVA and OVA+LPS, while FP did not reduce accumulations induced by OVA+LPS. Therefore, targeting SFKs may be a superior therapeutic approach for asthma exacerbation by infection.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Cytokines; Dasatinib; Disease Models, Animal; Fluticasone; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred BALB C; Ovalbumin

Asthma is a heterogeneous disease in which the complexity of the breathing pattern reduces as the severity of the disease increases. Since the pathophysiological basis of reduced breathing pattern complexity in asthma is unclear, in this study, we investigated the effect of reducing inflammation using an inhaled corticosteroid (fluticasone propionate) on the breathing pattern of a rat model of asthma. Detrended fluctuation analysis, sample entropy, and cross-sample entropy analysis of both inter-breath interval and respiratory volume time series showed that early treatment with inhaled corticosteroids not only diminishes lung inflammation and airway hyper-responsiveness, but also has a protective effect against the reduction of breathing pattern complexity due to asthma. However, late treatment had a partial effect on asthma-induced respiratory pattern changes. Since inflammation is a key factor in shifting breathing dynamics away from normal fluctuations, these findings further emphasize the importance of early treatment of asthma with corticosteroids.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Animals; Asthma; Fluticasone; Inflammation; Pneumonia; Rats; Respiration

The nano/micron sized-fluticasone propionate inhalable suspension (FPs) is used for asthma treatment, and this study aimed to elucidate the effects of particle size on the absorption of FPs by various pulmonary cells and the subsequent therapeutic efficacy for asthma. FPs of 727, 1136 and 1612 nm were prepared, and an increase in diameter diminished the endocytosis and macropinocytosis of FPs by alveolar epithelial cells (A549 and Calu-3 cells) but facilitated their uptake by M2-like macrophages; results about the transport across Calu-3 monolayer showed the mucus layer was the main rate-limiting step for the uptake of FPs by epithelial cells; the animal tests showed that although a decrease in diameter improved the pulmonary absorption of FPs, the particle size did not affect the lung distribution of FPs; a further detection revealed that larger FPs were taken more effectively by alveolar macrophages and lymphocytes and exerted a better therapeutic effect on asthma than the smaller ones. This study showed that the particle size of FPs had a significant impact on their absorption, elimination and cellular distribution in the lung after inhalation and further on their effectiveness in asthma treatment, and the particle size of the nano/micron sized-FPs should be designed and optimized for asthma treatment on the premise of meeting the requirements of inhalation preparations.

Topics: Administration, Inhalation; Androstadienes; Animals; Asthma; Fluticasone; Lung; Particle Size

The pathogenesis of asthma has been partially linked to lung and gut microbiome. We utilized a steroid-resistant chronic model of cockroach antigen-induced (CRA) asthma with corticosteroid (fluticasone) treatment to examine lung and gut microbiome during disease. The pathophysiology assessment demonstrated that mucus and airway hyperresponsiveness were increased in the chronic CRA with no alteration in the fluticasone (Flut)-treated group, demonstrating steroid resistance. Analysis of mRNA from lungs showed no decrease of MUC5AC or Gob5 in the Flut-treated group. Furthermore, flow-cytometry in lung tissue showed eosinophils and neutrophils were not significantly reduced in the Flut-treated group compared to the chronic CRA group. When the microbiome profiles were assessed, data showed that only the Flut-treated animals were significantly different in the gut microbiome. Finally, a functional analysis of cecal microbiome metabolites using PiCRUSt showed several biosynthetic pathways were significantly enriched in the Flut-treated group, with tryptophan pathway verified by ELISA with increased kynurenine in homogenized cecum samples. While the implications of these data are unclear, they may suggest a significant impact of steroid treatment on future disease pathogenesis through microbiome and associated metabolite pathway changes.

Topics: Allergens; Animals; Asthma; Cockroaches; Fluticasone; Lung; Microbiota

Brain functional deficits have been reported in asthma patients which can result in behavioral disorders like depression and anxiety. These deficits may be associated with factors like resistance to treatment, incorrect self-evaluation, and inadequate self-control. However, changes in the brain volume in allergic asthma and the effects of inhaled corticosteroids, the most common anti-inflammatory agents for asthma treatment, on these alterations remain largely unclear. Here, we evaluated depression and anxiety-like behavior as well as volume changes in different brain area, using magnetic resonance imaging in an animal model of allergic asthma with pretreatment of inhaled fluticasone propionate. Asthma-induced behavioral changes were partially, but not completely, prevented by pretreatment with inhaled fluticasone propionate. Volumetry findings showed that the allergen decreased volumes of the corpus callosum and subcortical white matter, as well as the septal region and hippocampus (especially CA1 and fimbria). However, volumes of neocortex, insular, and anterior cingulate cortex increased in asthmatic rats compared to controls. Namely, pretreatment with inhaled fluticasone propionate partially prevented asthma-induced brain volume changes, but not completely. These findings suggest that asthma is associated with structural alterations in the brain, which may contribute to the induction of psychological disorders. Thus, considering brain changes in the clinical assessments could have important implications for asthma treatment.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Animals; Anti-Asthmatic Agents; Anxiety; Asthma; Brain; Depression; Fluticasone; Rats

The objectives of this study were to quantify lymphocytes and eosinophils in the mucosa of the duodenum and rectum in asthmatic horses.. 8 healthy and 10 asthmatic horses.. Asthmatic horses were evaluated in a symptomatic (after 6 weeks of exposure to moldy hay) and asymptomatic status (3 and 7 months after being fed alfalfa pellets [n = 4] or treated with inhaled fluticasone [6]). Duodenal and rectal biopsies were endoscopically (n = 4 to 6) taken in each horse. Eosinophils were counted on slides stained with hematoxylin, eosin, phloxine, and saffron, and immunohistochemistry was used to evaluate T and B lymphocytes using CD3 and CD20, respectively.. The duodenal and rectal epithelium of asthmatic and control horses contained exclusively T lymphocytes (CD3). Symptomatic asthmatic horses, compared to controls, had a significantly higher number of T lymphocytes (CD3) in the duodenal epithelium (P = .016) and the adjacent lamina propria of the villi (P = .04). Compared to symptomatic asthmatic horses, the fluticasone-treated group had significantly fewer T lymphocytes in the total lamina propria of the rectal mucosa (P < .01).. Taken together, these results suggest that asthmatic horses have greater infiltration of T lymphocytes in the duodenal and rectal mucosa, indicating a certain degree of inflammation, which could be due to a systemic inflammatory effect and/or a local effect of ingested hay allergens in asthmatic horses. Systemic markers of inflammation have not been investigated to better qualify if the infiltration noted is due to a local and/or systemic effect.

Topics: Animals; Asthma; Duodenum; Fluticasone; Horse Diseases; Horses; Inflammation; Intestinal Mucosa; Lymphocytes; Rectum; T-Lymphocytes

This study compared the bronchoprotective and benefit/risk profiles of various inhaled corticosteroid (ICS) dosing regimens in mild asthma.. A pharmacokinetic/pharmacodynamic model was developed and validated describing the relationship between ICS dose and time-course for airway bronchoprotection, [provocative concentration of adenosine monophosphate (AMP) causing ≥ 20% decline in forced expiratory volume in 1 s (FEV. The model-predicted time course of ICS-induced bronchoprotection with regular daily maintenance dosing and 100% adherence showed that all ICS at the highest recommended doses for mild asthma exceeded the threshold for clinically significant bronchoprotective effect for all or most of the 28-day dosing period, mean (90% CI); 100% (96.1-100), 99.9% (8.0-100) and 100% (58.2-100) with TI values of 16.9, 6.6 and 5.4 for FF 100 µg OD, FP 200 µg BID and BUD 200 µg BID, respectively. For simulated poor adherence (50%) to regular daily maintenance therapy, corresponding mean (90% CI) values were; 75.7% (39.4-89.1), 52.3% (0.7-69.2) and 51.3% (28.6-58.3) with TI values of 25.7, 6.9 and 5.6. For simulated infrequent/as needed use the corresponding values were; 77.0% (37.6-87.0), 25.5% (0.0-38.0) and 26.2% (14.3-31.5) with TI values of 26.1, 6.7 and 5.7. For all regimen/scenarios, FF had the most sustained efficacy and favourable TI followed by FP and BUD.. At doses recommended for mild asthma, all ICS regimens provide sustained bronchoprotective efficacy when dosed regularly with high adherence. With poor adherence or use 3-4 times per week (infrequent/as needed), longer-acting ICS molecules will more likely provide sustained protection and a better TI versus shorter duration of action molecules (FF > FP ≥ BUD). These data highlight the benefits of using ICS as regular daily maintenance dosing in mild asthma and the potential risks of under-treatment with ICS (which may occur with ICS/formoterol as-needed approach in mild persistent asthma) associated with reduced levels of bronchoprotection.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Drug Combinations; Fluticasone; Humans; Risk Assessment

Apart from the individual diseases, some patients also show overlapping manifestations of asthma and COPD. Nevertheless, the diagnosis of COPD is often delayed due to inaccessibility to spirometry; the prevalence of the asthma COPD overlap phenotype is rather high given the exposure to biomass smoke. Furthermore, the rates of exacerbations are twice as high compared to the patients with either of the diseases. A treatment strategy that would reduce the risk of exacerbations would contribute immensely to the management of such patients. Evidence of eosinophilia (marker of inflammation) in patients with asthma, asthma COPD overlap phenotype or COPD alone should prompt treatment with a combination of inhaled corticosteroids (ICS)/ long-acting β-agonists (LABA); several studies have shown improvement in the airflow limitation and reduction in the rate of exacerbations with salmeterol-fluticasone combination (SFC). Considering the association of COPD and cardiovascular diseases (CVD), it is critical to determine the cardiovascular safety of the LABA in such patients. Salmeterol is a highly selective partial b-2 agonist; the TORCH study and the studies comparing formoterol and salmeterol infer that there is no increased risk of new cardiovascular adverse events either with Salmeterol or SFC. Furthermore, the combination may provide certain degree of cardio-protection. Since COPD per se increases the risk of CVD, the cardio-safety of salmeterol outweighs its onset of action. SFC has well substantiated benefits in patients with asthma, COPD and high-risk patients such as those with an overlap of COPD and asthma symptoms, patients with elevated eosinophils and pre-existing CVD. An advisory board was hence conducted, which discussed the role of combination of salmeterol and fluticasone (SFC) not only in asthma and COPD but also in asthma COPD overlap phenotype. Based on the panel's clinical experience and the expertise derived thereof, the propositions regarding the place of SFC therapy in patients with stable and uncontrolled asthma, asthma COPD overlap phenotype and COPD has been put forth.

Topics: Asthma; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate

Topics: Androstadienes; Asthma; Fluticasone; Humans

Non-T2 severe asthma and chronic obstructive pulmonary disease (COPD) are airway chronic inflammatory disorders with a poor response to corticosteroids. LAS194046, a novel pan-Janus kinase (JAK) inhibitor, shows inhibitory effects on T2 allergic lung inflammation in rats. In this work we analyze the effects of LAS194046, fluticasone propionate and their combination in neutrophils from non-T2 severe asthma and COPD patients in vitro. Neutrophils from 23 healthy subjects, 23 COPD and 21 non-T2 severe asthma patients were incubated with LAS194046 (0.01 nM-1 µM), fluticasone propionate (0.1 nM-1 µM) or their combination and stimulated with lipopolysaccharide (LPS 1 µM). LAS194046 shows similar maximal % inhibition and potency inhibiting IL-8, MMP-9 and superoxide anion release in neutrophils from healthy, COPD and asthma. Fluticasone propionate suppresses mediator release only in neutrophils from healthy patients. The combination of LAS194046 with fluticasone propionate shows synergistic anti-inflammatory and anti-oxidant effects. The mechanisms involved in the synergistic effects of this combination include the increase of MKP1 expression, decrease of PI3Kδ, the induction of glucocorticoid response element and the decrease of ERK1/2, P38 and JAK2/STAT3 phosphorylation compared with monotherapies. In summary, LAS194046 shows anti-inflammatory effects in neutrophils from COPD and severe non-T2 asthma patients and induces synergistic anti-inflammatory effects when combined with fluticasone propionate.

Topics: Administration, Inhalation; Androstadienes; Animals; Anti-Inflammatory Agents; Asthma; Fluticasone; Humans; Janus Kinase Inhibitors; Neutrophil Activation; Pulmonary Disease, Chronic Obstructive; Rats

Asthma and inflammatory airway diseases restrict airflow in the lung, compromising gas exchange and lung function. Inhaled corticosteroids (ICSs) can reduce inflammation, control symptoms, and improve lung function; however, a growing number of patients with severe asthma do not benefit from ICS. Using bronchial airway epithelial brushings from patients with severe asthma or primary human cells, we delineated a corticosteroid-driven fibroblast growth factor (FGF)-dependent inflammatory axis, with FGF-responsive fibroblasts promoting downstream granulocyte colony-stimulating factor (G-CSF) production, hyaluronan secretion, and neutrophilic inflammation. Allergen challenge studies in mice demonstrate that the ICS, fluticasone propionate, inhibited type 2-driven eosinophilia but induced a concomitant increase in FGFs, G-CSF, hyaluronan, and neutrophil infiltration. We developed a model of steroid-induced neutrophilic inflammation mediated, in part, by induction of an FGF-dependent epithelial-mesenchymal axis, which may explain why some individuals do not benefit from ICS. In further proof-of-concept experiments, we found that combination therapy with pan-FGF receptor inhibitors and corticosteroids prevented both eosinophilic and steroid-induced neutrophilic inflammation. Together, these results establish FGFs as therapeutic targets for severe asthma patients who do not benefit from ICS.

Topics: Adrenal Cortex Hormones; Animals; Asthma; Fibroblast Growth Factors; Fluticasone; Granulocyte Colony-Stimulating Factor; Humans; Hyaluronic Acid; Inflammation; Mice

To determine treatment persistence and exacerbations in patients initiating inhaler treatment with fixed-dose combinations of inhaled corticosteroids/long-acting beta-2-adrenergic agonists (ICS/LABA) for the treatment of asthma.. Retrospective observational study conducted by review of electronic medical records (database: Fundación RediSS).. Retrospective cohort study. The follow-up period was 1 year.. The study included patients aged ≥18 years who started treatment with ICS/LABA and met the inclusion/exclusion criteria.. The study groups were fluticasone propionate/salmeterol (FP/SAL), beclomethasone/formoterol (BDP/FORM), budesonide/formoterol (BUD/FORM), fluticasone furoate/vilanterol (FF/VI) and fluticasone propionate/formoterol (FP/FORM). The main measurements were persistence, medication possession ratio (MPR) and exacerbations. Statistical significance was established as p<0.05.. In total, 3203 patients were recruited for the study. By groups, 31.1% FP/SAL, 28.6% BDP/FORM, 25.0% BUD/FORM, 8.2% FF/VI and 7.0% FP/FORM. The mean age was 52.2 years, 60.8% were female and 44.9% had persistent-moderate asthma. Treatment persistence was 61.7% (95% CI 60.0% to 63.4%) and by study group it was FP/SAL: 60.7%, BDP/FORM: 61.2%, BUD/FORM: 60.3%, FF/VI: 66.7% and FP/FORM: 67.6% (p=0.046). MPR by study group was FP/SAL: 74.3%, BDP/FORM: 73.8%, BUD/FORM: 74.6%, FF/VI: 79.4% and FP/FORM: 80.6% (p=0.028). The mortality rate was 2.9%. By treatment group, exacerbations were FP/SAL: 21.9% (95% CI 19.3% to 24.5%), BDP/FORM: 22.2% (95% CI 19.5% to 24.9%), BUD/FORM: 22.8% (95% CI 19.9% to 25.7%), FF/VI: 17.9% (95% CI 14.9% to 20.7%) and FP/FORM: 16.0% (95% CI 12.2% to 19.3%), p=0.036.. Patients undergoing treatment with FP/FORM and FF/VI versus FP/SAL, BDP/FORM and BUD/FORM were associated with greater treatment adherence (persistence, MPR) and lower rates of exacerbations. However, further studies will be needed to strengthen the consistency of the results.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Anti-Asthmatic Agents; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Retrospective Studies

Outpatient treatment options for mild to moderate COVID-19 are severely limited. While many therapeutic options have been proposed, very few have demonstrated the appropriate safety and efficacy to warrant approval by national or international regulatory bodies. Monoclonal antibodies have been shown to decrease hospitalization in high-risk patients, but use remains limited due to challenges associated with both production and administration, and other treatment options are urgently needed. The anti-inflammatory drug fluticasone propionate has recently emerged as a potential outpatient treatment option, especially for those with newly diagnosed disease. This manuscript reviews what is known about fluticasone and looks ahead to examine how the drug may be used in the future to address the COVID-19 pandemic.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; COVID-19 Drug Treatment; Double-Blind Method; Fluticasone; Humans; Pandemics

Exposure to any form of glucocorticoid preparation is associated with a risk of adrenal insufficiency (AI).. To establish the contribution of oral corticosteroid (OCS) and inhaled corticosteroid (ICS) exposure to the risk of AI in a cohort of patients (n = 80) with severe, uncontrolled asthma.. We compiled individualized cumulative OCS and ICS exposure data using a combination of health care records and electronic inhaler monitoring using an Inhaler Compliance Assessment device and estimated the risk of AI for each participant using a morning serum cortisol concentration.. The predicted prevalence of AI based on morning cortisol concentrations was 25% (20 of 80). Participants on maintenance OCS therapy had the highest risk of AI at 60% (6 of 10) compared with 17% (11 of 65) in those with no recent OCS exposure. Morning serum cortisol correlated negatively with both OCS exposure (mg/kg prednisolone) (r = -0.4; P < .0002) and ICS exposure (mg/kg fluticasone propionate) (r = -0.26; P = .019). Logistic regression of risk of AI against the number of standard treatment courses of OCS demonstrated a positive relationship although this did not reach statistical significance (odds ratio, 1.41; 95% CI, 0.97-2.05; P = .073). Logistic regression analysis, categorizing patients as high-risk AI (cortisol <130 nmol/L) or not (cortisol >130 nmol/L), showed that cumulative ICS exposure remained a significant predictor of AI, even when exposure to OCS was controlled for (odds ratio, 2.17 per 1 mg/kg increase in cumulative fluticasone propionate exposure; 95% CI, 1.06-4.42; P = .033).. Our data suggest that AI is common among patients with asthma and highlights that the risk of AI is associated with both high-dose ICS therapy and intermittent treatment courses of OCS.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Anti-Asthmatic Agents; Asthma; Fluticasone; Glucocorticoids; Humans; Hydrocortisone; Prednisolone

To compare adherence and persistence among adult patients with asthma receiving single-inhaler FF/UMEC/VI versus multiple-inhaler triple therapy (MITT) in the United States.. This retrospective cohort study used IQVIA PharMetrics Plus data to evaluate patients with asthma who initiated once-daily FF/UMEC/VI 100/62.5/25 mcg or MITT between September 18, 2017, and September 30, 2019. Inverse probability weighting and multivariable regression adjusted for differences in characteristics between the FF/UMEC/VI and MITT cohorts. Adherence was assessed using proportion of days covered (PDC) and proportion of patients achieving PDC ≥0.8 and PDC ≥0.5. Non-persistence was identified as a >45-day gap between fills.. The study included 1396 FF/UMEC/VI and 5115 MITT initiators. Three months after initiation, FF/UMEC/VI users had significantly higher mean PDC versus MITT users (0.68 vs 0.59; P < .001) and 31% more likely to be adherent (PDC ≥0.8; 40.6% vs 31.3%; adjusted risk ratio [95% confidence interval (CI)]: 1.31 [1.13-1.54]; P < .001). Similar patterns were observed at 6 and 12 months post initiation. In addition, FF/UMEC/VI users were 49% more likely to persist at 12 months than MITT users (25.9% vs 15.1%, adjusted hazard ratio [95% CI]: 1.49 [1.39-1.60]; P < .001).. Patients with asthma initiating triple therapy with FF/UMEC/VI had significantly better adherence and persistence compared with MITT initiators.

Topics: Administration, Inhalation; Adult; Androstadienes; Asthma; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Drug Combinations; Fluticasone; Humans; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Retrospective Studies

Basic lung and heart ultrasound examination combined with chest X-ray (TUSX) is currently considered to be very useful for differentiation of asthma, chronic bronchitis and laryngeal paralysis from other diseases with dyspnea/coughing. Among 252 client-owned animals with persistent dyspnea/cough/noisy breathing, in 197 of them: pulmonary edema, pneumonia, lung cancer, free pleural fluid, pneumothorax, lung contusion or heart disease were diagnosed. The remaining 55 animals (42 dogs and 13 cats) were diagnosed with asthma (in 13 cats), chronic bronchitis (in 37 dogs) and laryngeal paralysis (in 5 dogs) using TUSX. These animals were qualified for inhaled fluticasone treatment using 3 types of spacers - two commercial and a home- -made mask. 36 animals (65.5%) completed the trail. In 26 of them (72.2%) the owners observed complete, long lasting relief of the symptoms, and the owners of 7 animals (19.5%) declared a considerable clinical improvement, regardless of the type of spacer used. The owners of 3 animals (8.3%) did not see any improvement. The proposed diagnostic and therapeutic management improved long-term clinical status of the vast majority (91.7%) of animals. Therefore, it seems justified to include the TUSX diagnostic protocol in daily veterinary practice and to encourage owners to prepare home-made face masks for inhaled fluticasone treatment.

Topics: Animals; Asthma; Bronchitis, Chronic; Cat Diseases; Cats; Dog Diseases; Dogs; Dyspnea; Fluticasone; Lung; Vocal Cord Paralysis; X-Rays

The respiratory system has generated significant interest as an alternative drug delivery route. However, because of the limitations encountered with the present inhalation devices, alternative options could present an ideal opportunity to enhance therapeutic effectiveness and patient compliance. Vaping devices have been extensively used to deliver nicotine. This manuscript aimed to conduct an

Topics: Administration, Inhalation; Asthma; Drug Delivery Systems; Fluticasone; Humans; Lung; Metered Dose Inhalers; Nicotine; Vaping

To observe the clinical efficacy of self-made Lifei Dingchuan decoction combined with western medicine in the treatment of cough variant asthma (phlegm-heat accumulation in the lung syndrome).. The clinical data of 90 patients with cough variant asthma who were hospitalized in the Department of Respiratory Medicine of our hospital from January 2020 to April 2022 were selected as the research objects, and they were equally divided into the observation group and the reference group according to different treatment methods, 45 cases in each group. The group was treated with traditional montelukast sodium chewable tablet and salmeterol fluticasone mixed powder inhalation, and the observation group was treated with self-made Lifei Dingchuan decoction on the basis of the control group, saturation, pH, partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide, length of stay, and hospitalization costs.. After the patients underwent self-made Lifei Dingchuan decoction, there were significant differences between the observation group and the reference group in terms of heart rate, respiratory rate, blood oxygen saturation, pH value, arterial blood oxygen partial pressure, carbon dioxide partial pressure, and within the group. There was a statistical difference (. The study on the clinical efficacy and low hospitalization cost of the self-prepared lung and asthma-restorative soup in patients with cough variant asthma significantly improved the patients' arterial oxygen saturation, acid-base value, arterial partial pressure of oxygen, and partial pressure of carbon dioxide and effectively controlled the heart rate and respiratory rate with high safety, which is worth further promotion.

Topics: Acetates; Asthma; Carbon Dioxide; Cough; Cyclopropanes; Fluticasone; Humans; Oxygen; Powders; Quinolines; Salmeterol Xinafoate; Sulfides; Tablets

Inhaled corticosteroids (ICS) are commonly prescribed first-line treatments for asthma and chronic obstructive pulmonary disease (COPD). Recent evidence has shown that ICS use is associated with changes in the airway microbiome, which may impact clinical outcomes such as potential increased risk for pneumonia in COPD. Although the immunomodulatory effects of corticosteroids are well appreciated, whether ICS could directly influence the behavior of respiratory tract bacteria has been unknown. In this pilot study we explored the effects of fluticasone proprionate, a commonly prescribed inhaled corticosteroid, on respiratory bacteria with an expanded focus on Klebsiella pneumoniae, a species previously implicated in fluticasone-associated pneumonia in COPD. We observed significant effects of fluticasone proprionate on growth responses of

Topics: Adrenal Cortex Hormones; Asthma; Fluticasone; Humans; Klebsiella pneumoniae; Pilot Projects; Pneumonia; Pulmonary Disease, Chronic Obstructive

Fluticasone propionate/salmeterol multidose, dry powder inhaler (MDPI) was the first and only authorized generic inhaled corticosteroid/long-acting beta agonist (ICS/LABA) combination inhaler at the time of this study. This offers the potential for significant prescription cost-savings for both patients and accountable care organizations. The objective of the study was to demonstrate patients' clinical response to generic fluticasone propionate/salmeterol MDPI when switched from one of its brand name competitors.. The study was approved by the Institutional Review Board at MCPHS University. This was a prospective chart review of a large, multi-center ambulatory care organization in the Greater Boston area. Patients 12 years of age or older who were switched from a brand-name ICS/LABA inhaler to the generic fluticasone/salmeterol MDPI were included in the study. The primary endpoint was worsened asthma control requiring a change in therapy, oral corticosteroid therapy, or hospitalization at or before 12 weeks after the inhaler was switched.. In total, 203 patients met inclusion criteria. Of those 203 patients, 35 had a change in therapy due to worsened asthma control (17.2% of patients, 95% CI 12.0% to 22.4%) within 12 weeks. Total projected yearly prescription cost-savings for patients who were switched and remained on the generic inhaler was $581,628.. Eighty-three percent of patients maintained appropriate asthma control after switching from a brand ICS/LABA inhaler to the generic fluticasone/salmeterol MDPI for 12 weeks. Switching to the generic inhaler resulted in significant prescription cost-savings for the accountable care organization.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Ambulatory Care; Asthma; Bronchodilator Agents; Drug Combinations; Drugs, Generic; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Nebulizers and Vaporizers; Powders; Propionates; Prospective Studies; Salmeterol Xinafoate

Topics: Asthma; Beclomethasone; Fluticasone; Humans; Propionates

Pharmacogenetic studies in asthma cohorts, primarily made up of White people of European descent, have identified loci associated with response to inhaled beta agonists and corticosteroids (ICSs). Differences exist in how individuals from different ancestral backgrounds respond to long-acting beta agonist (LABA) and ICSs. Therefore, we sought to understand the pharmacogenetic mechanisms regulating therapeutic responsiveness in individuals of African descent.. We did ancestry-based pharmacogenetic studies of children (aged 5-11 years) and adolescents and adults (aged 12-69 years) from the Best African Response to Drug (BARD) trials, in which participants with asthma uncontrolled with low-dose ICS (fluticasone propionate 50 μg in children, 100 μg in adolescents and adults) received different step-up combination therapies. The hierarchal composite outcome of pairwise superior responsiveness in BARD was based on asthma exacerbations, a 31-day difference in annualised asthma-control days, or a 5% difference in percentage predicted FEV. We included 249 unrelated children and 267 unrelated adolescents and adults in the BARD pharmacogenetic analysis. In children, we identified a significant admixture mapping peak for superior responsiveness to 5 × ICS versus 100 μg fluticasone plus salmeterol on chromosome 12 (odds ratio [OR. BARD is the first genome-wide pharmacogenetic study of LABA and ICS response in clinical trials of individuals of African descent to detect and replicate genome-wide significant loci. Admixture mapping of the composite BARD trial outcome enabled the identification of novel pharmacogenetic variation accounting for differential therapeutic responses in people of African descent with asthma.. National Institutes of Health, National Heart, Lung, and Blood Institute.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Asthma; Black People; Bronchodilator Agents; Child; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Pharmacogenomic Testing; Salmeterol Xinafoate; United States; Young Adult

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Double-Blind Method; Fluticasone; Humans

Allergic asthma, typically controlled with inhaled corticosteroids (ICS), is the leading chronic health condition for youth under 18 years of age. During this peri-adolescent period, significant brain maturation occurs. Prior studies indicate that both chronic inflammation and corticosteroid medications increase risk for developing an internalizing disorder like anxiety.. To determine if chronic ICS treatments exacerbate or alleviate anxiety symptoms associated with developmental allergic asthma, we used a mouse model to isolate the influence of ICS (fluticasone propionate, FLU) vs. airway inflammation (induced with house dust mite extract, HDM).. During development, male and female BALB/cJ mice were repeatedly exposed to HDM or saline plus one of four FLU doses (none/vehicle, low, moderate, or high). In adulthood, we assessed lung inflammation, circulating and excreted corticosteroids, anxiety-like behavior, and gene expression in stress and emotion regulation brain regions.. FLU treatment decreased body weight and anxiety-like behavior and increased fecal corticosterone metabolite concentrations and Crhr2 gene expression in ventral hippocampus. FLU effects were only observed in saline/non-HDM-exposed mice, and the FLU doses used did not significantly decrease HDM-induced airway inflammation. Females had greater serum and fecal corticosterone concentrations, less anxiety-like behavior, and lower Crhr1 gene expression in ventral hippocampus and prefrontal cortex than males.. These findings suggest that steroid medications for youth with allergic asthma may not exacerbate anxiety-related symptoms, and that they should be avoided in children/adolescents without a health condition. The results are informative to future work on the use of corticosteroid medications during childhood or adolescent development.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aging; Allergens; Animals; Anxiety; Asthma; Disease Models, Animal; Female; Fluticasone; Humans; Inflammation; Male; Mice; Mice, Inbred BALB C; Pyroglyphidae

The aim of this study was to measure the concentration of FeNO in asthmatics with and without allergic rhinitis (AR) and to determine usefulness of the test in the assessment of asthma control in the Polish population. The next objective of this study was to estimate the cut-off point of FeNO which might be a good indicator of uncontrolled asthma.. The measurements were taken using the Hyp'Air FeNO in 303 adult patients with asthma, AR, comorbid AR and asthma, and non-diseased volunteers.. FeNO level in healthy adults was similar to the FeNO concentration in AR as well as controlled asthmatic patients without and with AR. Patients with partly controlled and uncontrolled asthma with and without AR had higher FeNO (>60 ppb) levels when compared to adults with controlled disease. The optimal cut-off point of FeNO > 46 ppb and FeNO > 33 ppb was estimated for identification of uncontrolled asthmatics without and with AR, respectively.. In conclusion, we found a significant correlation between the FeNO concentration and the level of asthma symptom control in asthmatic patients with and without AR.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Asthma; Biomarkers; Breath Tests; Bronchodilator Agents; Budesonide; Case-Control Studies; Exhalation; Female; Fluticasone; Humans; Male; Middle Aged; Nitric Oxide; Rhinitis, Allergic; Salmeterol Xinafoate; Spirometry

Inhaled fluticasone is used in asthma for long duration. However, it's adverse effect on glycaemia is debatable. This study observed the outcome of inhaled fluticasone in asthma patients. A cross sectional comparative study was conducted among the normoglycaemic asthma patients aged 18 years and above attending outpatient department of Internal Medicine and Respiratory Medicine department of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from June 2017 to May 2018. Study group were getting inhaled fluticasone for minimum three months whereas comparative group were not on any steroids. Each group had 35 eligible participants (n=70). Spirometry and plasma glucose at fasting and 2-hour after 75gm oral glucose intake were measured along with HbA1c%. Statistical analysis was done using SPSS 21.0. In study group mean plasma glucose at fasting was 5.27±0.48mmol/L, 2-hour after 75gm oral glucose was 6.04±1.21mmol/L and mean of HbA1c was 5.57±0.41% whereas in comparative group these were5.17±0.59mmol/L, 5.69±1.09mmol/L, 5.47±0.40% respectively (p=0.25, 0.20, 0.75 respectively). There was no specific co-relation between duration of use of fluticasone inhaler and glycaemic parameters like plasma glucose at fasting, 2-hour after 75gm oral glucose and HbA1c% (r=0.016, p=0.46; r=0.015, p=0.47; r=0.019, p=0.42 respectively). Use of inhaled fluticasone for 3months or more has insignificant effect on plasma glucose levels of asthma patients. Duration of use of inhaled fluticasone has no specific correlation with plasma glucose and HbA1c values.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Bangladesh; Cross-Sectional Studies; Double-Blind Method; Fluticasone; Humans

Daily inhaled corticosteroids (ICSs) are fundamental to asthma management, but adherence is low.. To investigate (1) whether LC-MS/MS could be used to detect ICSs in serum and (2) whether serum levels related to markers of disease severity.. We collected blood samples over an 8-hour period from patients with severe asthma prescribed at least 1000 μg daily of beclomethasone dipropionate equivalent. Following baseline sampling, patients were observed taking their usual morning dose. Subsequent blood samples were obtained 1, 2, 4, and 8 hours postinhalation and analyzed by LC-MS/MS. Correlations between serum ICS levels and severity markers were investigated.. A total of 60 patients were recruited (41 females; 39 prescribed maintenance prednisolone; mean age, 49 ± 12 years; FEV. Commonly used ICSs can be reliably detected in the blood at least 8 hours after dosing, and could therefore be used as a measure of adherence in severe asthma. Higher exacerbation rates and poorer lung function (for fluticasone propionate) were associated with lower blood levels.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Chromatography, Liquid; Female; Fluticasone; Humans; Middle Aged; Tandem Mass Spectrometry

Spirometry is a crucial test used in the diagnosis and monitoring of patients with chronic obstructive pulmonary disease (COPD). Severe acute respiratory syndrome coronavirus 2 pandemic has posed numerous challenges in performing spirometry. Dynamic-ventilatory digital radiography (DR) provides sequential chest radiography images during respiration with lower doses of radiation than conventional X-ray fluoroscopy and computed tomography. Recent studies revealed that parameters obtained from dynamic DR are promising for evaluating pulmonary function of COPD patients. We report two cases of COPD evaluated by dynamic-ventilatory DR for pulmonary function and treatment efficacy and discuss the potential of dynamic DR for evaluating COPD therapy.

Topics: Aged; Asthma; Bronchodilator Agents; Drug Combinations; Fluticasone; Formoterol Fumarate; Glycopyrrolate; Humans; Indans; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Radiographic Image Enhancement; Radiography, Thoracic; Spirometry; Tiotropium Bromide; Treatment Outcome

Topics: Animals; Asthma; Autophagy; Female; Fluticasone; Kinetics; Lysosomes; Macrolides; Mice; Mice, Inbred BALB C; Vacuolar Proton-Translocating ATPases

Abnormal peripheral airway function is an important feature of asthma and relates to asthma symptoms and poor asthma control. We aimed to determine whether peripheral airway function, as measured by forced oscillatory impedance and multiple-breath nitrogen washout (MBNW), relates to symptom improvement in asthmatic participants with uncontrolled asthma, after stepping up to high-dose ICS/LABA treatment.. Step-up to high-dose combination treatment in uncontrolled asthma is associated with improved peripheral airway function as measured by Xrs

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Drug Combinations; Female; Fluticasone; Formoterol Fumarate; Humans; Lung; Male; Nitrogen; Oscillometry; Pulmonary Ventilation; Respiration; Respiratory Function Tests; ROC Curve; Spirometry

Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Fluticasone; Humans

The increase in life expectancy with the advent of highly effective antiretroviral therapy poses challenges in terms of toxicity and drug interactions. Exogenous Cushing syndrome by interaction between ritonavir and inhaled fluticasone in children diagnosed with human immunodeficiency virus infection and chronic pulmonary pathology is rare. So far, there are 20 cases reported. Three pediatric cases are reported, with a diagnosis of human immunodeficiency virus infection and chronic pulmonary pathology who presented exogenous Cushing syndrome with inhaled fluticasone at usual doses due to drug interaction between it and ritonavir. The patients resolved the clinical picture after 2-4 months of fluticasone suspension and remain asymptomatic in the follow-up.. El incremento de la expectativa de vida con el advenimiento de la terapia antirretroviral de alta eficacia plantea desafíos en cuanto a la toxicidad e interacciones medicamentosas. El síndrome de Cushing exógeno por interacción entre ritonavir y fluticasona inhalada en niños con diagnóstico de infección por virus de la inmunodeficiencia humana y patología pulmonar crónica es infrecuente. Hasta el momento, hay 20 casos reportados. Se describen 3 casos pediátricos con diagnóstico de infección por virus de la inmunodeficiencia humana y patología pulmonar crónica que presentaron síndrome de Cushing exógeno con fluticasona inhalada en dosis habituales por la interacción medicamentosa entre esta y ritonavir. Los pacientes resolvieron el cuadro clínico luego de 2-4 meses de suspensión de la fluticasona y permanecieron asintomáticos en el seguimiento.

Topics: Administration, Inhalation; Adolescent; Anti-HIV Agents; Asthma; Bronchodilator Agents; Child; Chronic Disease; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Infections; Humans; Lung Diseases, Interstitial; Male; Ritonavir

Topics: Animals; Antithrombins; Asthma; Biomarkers; Bronchoalveolar Lavage Fluid; Chemokine CXCL1; Dabigatran; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Fluticasone; Inflammation; Inflammation Mediators; Lipopolysaccharides; Male; Mice, Inbred Strains; Osteopontin; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha

Bronchial asthma (BA) is a chronic airway inflammatory disease with reversible airflow limitation as the main clinical manifestations, such as wheezing, cough, shortness of breath, chest tightness, etc, mediated by a variety of inflammatory cells, which can be recurrent. Clinical can improve symptoms, but cannot be cured; glucocorticoid is the most important first-line medication. Clinical practice has shown that montelukast sodium combined with fluticasone in the treatment of adult BA can improve clinical efficacy and reduce adverse reactions. The purpose of this study is to systematically study the efficacy and safety of montelukast sodium combined with fluticasone in the treatment of adult BA.. The Chinese databases (CNKI, VIP, Wanfang, Chinese Biomedical Database) and English databases (PubMed, the Cochrane Library, Embase, Web of Science) were searched by computer, for the randomized controlled clinical studies of montelukast sodium combined with fluticasone in the treatment of adult BA from establishment of database to October 2020. Two researchers independently extracted the relevant data and evaluated the quality of the literatures, and used RevMan5.3 software to conduct meta-analyze of the included literatures.. This study assessed the efficacy and safety of montelukast sodium combined with fluticasone in the treatment of adult BA through total effective rate, pulmonary function (FEV1, FVC, PEF, FEV1/FVC), and adverse reactions.. This study will provide reliable evidence-based evidence for the clinical application of montelukast sodium combined with fluticasone in the treatment of adult BA.. DOI 10.17605/OSF.IO/CKQFM.

Topics: Acetates; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Cyclopropanes; Drug Combinations; Fluticasone; Humans; Meta-Analysis as Topic; Quinolines; Research Design; Sulfides; Systematic Reviews as Topic; Treatment Outcome

Inhaled corticosteroids (ICS) are the mainstay of asthma treatment, but evidence suggests a link between ICS usage and increased rates of respiratory infections. We assessed the composition of the asthmatic airways microbiome in asthma patients taking low and high dose ICS and the stability of the microbiome over a 2 week period.. We prospectively recruited 55 individuals with asthma. Of these, 22 were on low-dose ICS and 33 on high-dose ICS (16 on budesonide, 17 on fluticasone propionate). Sputum from each subject underwent DNA extraction, amplification and 16S rRNA gene sequencing of the bacterial component of the microbiome. 19 subjects returned for further sputum induction after 24 h and 2 weeks.. A total of 5,615,037 sequencing reads revealed 167 bacterial taxa in the asthmatic airway samples, with the most abundant being Streptococcus spp. No significant differences in sputum bacterial load or overall community composition were seen between the low- and high-dose ICS groups. However, Streptococcus spp. showed significantly higher relative abundance in subjects taking low-dose ICS (p = 0.002). Haemophilus parainfluenzae was significantly more abundant in subjects on high-dose fluticasone propionate than those on high-dose budesonide (p = 0.047). There were no statistically significant changes in microbiota composition over a 2-week period.. Whilst no significant differences were observed between the low- and high-dose ICS groups, increased abundance of the potential pathogen H. parainfluenzae was observed in patients taking high-dose fluticasone propionate compared to those taking high-dose budesonide. The microbiota were stable over fourteen days, providing novel evidence of the established community of bacteria in the asthmatic airways.. ClinicalTrials.gov NCT02671773.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Budesonide; Dose-Response Relationship, Drug; Fluticasone; Humans; Microbiota; Middle Aged; Prospective Studies; Respiratory Tract Infections; Sputum; Young Adult

Pneumonia is an important cause of morbidity and mortality. COPD patients using inhaled corticosteroids (ICS) have an increased risk of pneumonia, but less is known about whether ICS treatment in asthma also increases the risk of pneumonia. The aim of this analysis was to examine risk factors for hospitalisations with pneumonia in a general population sample with special emphasis on asthma and the use of ICS in asthmatics.. In 1999 to 2000, 7340 subjects aged 28 to 54 years from three Swedish centres completed a brief health questionnaire. This was linked to information on hospitalisations with pneumonia from 2000 to 2010 and treatment with ICS from 2005 to 2010 held within the Swedish National Patient Register and the Swedish Prescribed Drug Register.. Participants with asthma (n = 587) were more likely to be hospitalised with pneumonia than participants without asthma (Hazard Ratio (HR 3.35 (1.97-5.02)). Other risk factors for pneumonia were smoking (HR 1.93 (1.22-3.06)), BMI < 20 kg/m2 (HR 2.74 (1.41-5.36)) or BMI > 30 kg/m2 (HR 2.54 (1.39-4.67)). Asthmatics (n = 586) taking continuous treatment with fluticasone propionate were at an increased risk of being hospitalized with pneumonia (incidence risk ratio (IRR) 7.92 (2.32-27.0) compared to asthmatics that had not used fluticasone propionate, whereas no significant association was found with the use of budesonide (IRR 1.23 (0.36-4.20)).. Having asthma is associated with a three times higher risk of being hospitalised for pneumonia. This analysis also indicates that there are intraclass differences between ICS compounds with respect to pneumonia risk, with an increased risk of pneumonia related to fluticasone propionate.

Topics: Administration, Inhalation; Adult; Asthma; Budesonide; Female; Fluticasone; Glucocorticoids; Hospitalization; Humans; Male; Middle Aged; Obesity; Pneumonia; Proportional Hazards Models; Risk Factors; Smoking; Sweden; Thinness

Variability in response to inhaled corticosteroids (ICSs) can result in less than optimal asthma control. Development of biomarkers assessing the therapeutic efficacy of corticosteroids is important.. We sought to examine whether in vitro PBMC responses to corticosteroids relate to the clinical ICS response.. Compared with PBMCs from patients with easy-to-control asthma, PBMCs from those with difficult-to-control asthma had significantly lower glucocorticoid receptor α levels at V0 (P = .05). A 30% increase in IL-8 suppression by FLU (P = .04) and a trend for increased TNF-α suppression by FLU between V0 and V6 (P = .07) were observed in patients with easy-to-control asthma. In contrast, no changes between V0 and V6 in IL-8 and TNF-α suppression by FLU were observed in patients with difficult-to-control asthma. Corticosteroid-mediated transactivation (FK506-binding protein 5 induction by FLU) increased in the PBMCs of patients with difficult-to-control and easy-to-control asthma between V0 and V6 (P = .05 and P = .03, respectively).. PBMCs of children with difficult-to-control asthma treated with guidelines-based therapy and requiring high-dose ICSs had reduced in vitro responsiveness to corticosteroids.

Topics: Adolescent; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Cells, Cultured; Child; Female; Fluticasone; Gene Expression Regulation; Humans; Interleukin-8; Leukocytes, Mononuclear; Male; Receptors, Glucocorticoid; Tacrolimus Binding Proteins; Tumor Necrosis Factor-alpha; Vitamin D3 24-Hydroxylase

Rhinitis and asthma are linked, but substantial knowledge gaps in this relationship exist.. We sought to determine the prevalence of rhinitis and its phenotypes in children and adolescents with asthma, assess symptom severity and medication requirements for rhinitis control, and investigate associations between rhinitis and asthma.. Seven hundred forty-nine children with asthma participating in the Asthma Phenotypes in the Inner-City study received baseline evaluations and were managed for 1 year with algorithm-based treatments for rhinitis and asthma. Rhinitis was diagnosed by using a questionnaire focusing on individual symptoms, and predefined phenotypes were determined by combining symptom patterns with skin tests and measurement of serum specific IgE levels.. Analyses were done on 619 children with asthma who completed at least 4 of 6 visits. Rhinitis was present in 93.5%, and phenotypes identified at baseline were confirmed during the observation/management year. Perennial allergic rhinitis with seasonal exacerbations was most common (34.2%) and severe. Nonallergic rhinitis was least common (11.3%) and least severe. The majority of children remained symptomatic despite use of nasal corticosteroids with or without oral antihistamines. Rhinitis was worse in patients with difficult-to-control versus easy-to-control asthma, and its seasonal patterns partially corresponded to those of difficult-to-control asthma.. Rhinitis is almost ubiquitous in urban children with asthma, and its activity tracks that of lower airway disease. Perennial allergic rhinitis with seasonal exacerbations is the most severe phenotype and most likely to be associated with difficult-to-control asthma. This study offers strong support to the concept that rhinitis and asthma represent the manifestations of 1 disease in 2 parts of the airways.

Topics: Adolescent; Adrenergic beta-2 Receptor Agonists; Anti-Allergic Agents; Asthma; Bronchodilator Agents; Child; Female; Fluticasone; Humans; Male; Phenotype; Prevalence; Rhinitis; Salmeterol Xinafoate; Severity of Illness Index

There have been concerns about the risk of inhaled corticosteroid (ICS)-related tuberculosis (TB) development.. We investigated the occurrence of TB among ICS users according to underlying respiratory diseases and type of ICS.. A 12-year population cohort comprising approximately 1 million subjects collected from the Korean claims database were used. Adult ICS users (budesonide or fluticasone) were enrolled. The temporal relationship between TB development and the last ICS prescription before TB development was evaluated. A nested case-control study was performed with 1:4 matching for age, sex, and the initiation date of the ICS.. There were 17,991 ICS users, and 175 developed TB during the study period. Approximately 80% (140/175) of patients who developed TB were diagnosed within 3 years after the last ICS prescription. In the nested case-control study, the occurrence of TB was not related to the type of ICS, but was related to a higher annual admission rate and a higher comorbidity score. The risk of TB was higher in patients with chronic obstructive pulmonary disease (COPD) than in those with asthma (odds ratio: 2.31; CI 95%: 1.39-3.38; P = .0011) after adjusting for covariates. The subgroup analysis revealed no difference between budesonide and fluticasone with respect to the risk of developing TB in patients with asthma, COPD, or asthma-COPD overlap syndrome.. An increased risk of TB development may persist for 3 years after stopping the ICS and the risk is higher in patients with COPD regardless of the type of ICS used.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Asthma; Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome; Budesonide; Case-Control Studies; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; Logistic Models; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Republic of Korea; Risk Factors; Tuberculosis; Tuberculosis, Pulmonary; Young Adult

Fluticasone propionate uptake in the presence of a proprietary cell-penetrating peptide (human stimulus factor, [HSF]) based on the N-terminal domain of lactoferrin was studied, alone and in combination with salmeterol, using an air interface Calu-3 epithelial model. The HSF enhanced uptake and transport of fluticasone propionate across the epithelial barrier when alone and in presence of salmeterol. This was attributed to transcellular-mediated uptake. This HSF is a promising peptide for delivery of therapeutics where enhanced epithelial penetrating is required.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Cell Line, Tumor; Cell Membrane; Drug Carriers; Drug Combinations; Fluticasone; Humans; Lactoferrin; Peptides; Permeability; Protein Domains; Pulmonary Disease, Chronic Obstructive; Respiratory Mucosa; Salmeterol Xinafoate

Steroid insensitivity constitutes a major problem for asthma management. Toluene diisocyanate (TDI) is one of the leading allergens of asthma that induces both T-helper Th2 and Th17 responses, and is often associated with poor responsiveness to steroid treatment in the clinic.We sought to evaluate the effects of inhaled and systemic steroids on a TDI-induced asthma model and to find how interleukin (IL)-17A and IL-17F function in this model. BALB/c mice were exposed to TDI for generating an asthma model and were treated with inhaled fluticasone propionate, systemic prednisone, anti-IL-17A, anti-IL-17F, recombinant IL-17A or IL-17F.Both fluticasone propionate and prednisone showed no effects on TDI-induced airway hyperresponsiveness (AHR), bronchial neutrophilia and eosinophilia, and epithelial goblet cell metaplasia. TDI-induced Th2 and Th17 signatures were not suppressed by fluticasone propionate or prednisone. Treatment with anti-IL-17A after TDI exposure led to increased AHR, aggravated mucus production and airway eosinophil recruitment, accompanied by amplified Th2 responses, whereas anti-IL-17F ameliorated TDI-induced AHR and airway neutrophilia, with decreased Th17 responses. Recombinant IL-17A and IL-17F showed opposite effects to the monoclonal antibodies.IL-17A and IL-17F exert distinct biological effects during airway inflammation of a TDI-induced asthma model, which is unresponsive to both inhaled and systemic steroids.

Topics: Animals; Asthma; Bronchodilator Agents; Disease Models, Animal; Drug Resistance; Fluticasone; Glucocorticoids; Interleukin-17; Mice; Mice, Inbred BALB C; Prednisone; Toluene 2,4-Diisocyanate

Bronchial thermoplasty is a nonpharmacological treatment for severe asthma that delivers thermal energy to the bronchial walls and reduces hypertrophied smooth muscle mass. Previous studies have shown its efficacy and safety, resulting in approval from the Food and Drug Administration in 2010. In Korea, the first bronchial thermoplasty was carried out in 2014; 4 patients have undergone the procedure so far. This case series presents the medical history and treatment outcomes of these 4 patients. All patients presented with uncontrolled asthma despite optimal medical treatment. Bronchial thermoplasty was performed at the right lower lobe, left lower lobe, and both upper lobes in order at 3-week intervals. All procedures were performed under general anesthesia. Two patients had significant decreases in exacerbations and required a lower dose of inhaled corticosteroids after the procedure. One patient had slightly fewer exacerbations but failed to reduce the use of systemic corticosteroids. One patient had no change in symptoms. One limitation of bronchial thermoplasty is the difficulty of predicting clinical responders. However, since more therapeutic options are needed in the management of severe asthma, especially T2-low asthma, discussion with experts about the feasibility and necessity of bronchial thermoplasty will ensure the best possible care.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Bronchial Thermoplasty; Bronchoscopy; Female; Fluoroquinolones; Fluticasone; Forced Expiratory Volume; Humans; Male; Middle Aged; Republic of Korea; Salmeterol Xinafoate; Severity of Illness Index; Tomography, X-Ray Computed

Oral PI3Kδ inhibitors such as Idelalisib and Duvelisib have shown efficacy as anticancer agents and Idelalisib has been approved for the treatment of three B-cell cancers. However, Idelalisib has a black box warning on its product label regarding the risks of fatal and serious toxicities including hepatic toxicity, severe diarrhea, colitis, pneumonitis, infections, and intestinal perforation. Some of these side effects are mechanism-related and could hinder the development of Idelalisib for less severe conditions. For respiratory diseases, compounds administered by inhalation are delivered directly to the site of action and may improve the therapeutic index of a drug, minimizing undesired side effects. This work describes the discovery and optimization of inhaled PI3Kδ inhibitors intended for the treatment of severe asthma and COPD. Once the potency was in the desired range, efforts were focused on identifying the particular physicochemical properties that could translate into better lung retention. This medicinal chemistry exercise led to the identification of LAS195319 as a candidate for clinical development.

Topics: Administration, Inhalation; Asthma; Class I Phosphatidylinositol 3-Kinases; Dose-Response Relationship, Drug; Drug Discovery; Enzyme Inhibitors; Humans; Inhibitory Concentration 50; Models, Molecular; Protein Conformation; Pulmonary Disease, Chronic Obstructive

Asthma is the most common chronic respiratory disease in children and inhaled corticosteroids (ICS) constitute the first line of treatment for these patients. However, the potential growth-inhibiting effect of ICS has often been a cause of concern for both caregivers as well as physicians, and there still remains conflict regarding their safety profile.. To assess whether the administration of ICS in low or medium doses is associated with height reduction in prepubertal children.. We performed a retrospective study to examine the association between ICS treatment and growth deceleration in children with mild persistent asthma. The comparison of height measurements every 6 months from 3 to 8 years of age was conducted among three groups of patients: patients not receiving ICS, patients being treated with low dose of ICS and patients being treated with medium dose of ICS (GINA Guidelines 2015).. This study included 284 patients (198 male, 86 female) aged 3-8 years; 75 patients were not receiving ICS, 63 patients were on low-dose ICS and 146 patients were on medium-dose ICS. The measured height every 6 months did not differ significantly (p > 0.05) among the three groups while the difference remained stable (p > 0.05), even when we evaluated males and females separately.. In this "real-life" study we found that long-term treatment with ICS in low or medium doses is not associated with height reduction in prepubertal children with asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Body Height; Child; Child, Preschool; Female; Fluticasone; Humans; Male; Retrospective Studies; Sexual Development

Inhaled corticosteroids are used to treat pediatric asthma. The shaking of a pressurized metered-dose inhaler (pMDI) is required to ensure consistency of emitted dose. Delays between shaking and actuating the pMDI are frequent during administration of aerosols to children where a valved holding chamber is used.. In a recent clinical trial, we used a monitoring device to record shaking and actuation of the pMDI and the inhalation profiles of children with asthma while they were inhaling fluticasone hydrofluoroalkane from a valved holding chamber onto an external filter. During the procedure, in vitro and transport samples were generated without a delay between shaking and actuating the pMDI. Emitted dose, expressed as percentage of ex-actuator nominal dose, obtained from the second actuation following a recorded shake-actuation interval for subjects and from in vitro/transport samples (no delay) were compared.. The mean emitted dose was 158.6% (95% CI 150.1-167.2%) (subjects) and 106.8% (95% CI 104.7-108.9%) (in vitro + transport) of the ex-actuator nominal dose (. Delays between shaking and actuating a corticosteroid suspension pMDI resulted in an increase in the emitted dose of the second actuation following the delay. This can be a common occurrence when doses are administered by a caregiver to a patient via a holding chamber. This should be addressed by practitioners educating patients and parents on proper inhaler use. (ClinicalTrials.gov registration NCT01714063.).

Topics: Administration, Inhalation; Aerosols; Asthma; Bronchodilator Agents; Child; Child, Preschool; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Pressure; Random Allocation; Time Factors

Establishing a comprehensive clinical evaluation system is critical in enacting national drug policy and promoting rational drug use. In China, the 'Clinical Comprehensive Evaluation System for Pediatric Drugs' (CCES-P) project, which aims to compare drugs based on clinical efficacy and cost effectiveness to help decision makers, was recently proposed; therefore, a systematic and objective method is required to guide the process.. An evidence-based multi-criteria decision analysis model that involved an analytic hierarchy process (AHP) was developed, consisting of nine steps: (1) select the drugs to be reviewed; (2) establish the evaluation criterion system; (3) determine the criterion weight based on the AHP; (4) construct the evidence body for each drug under evaluation; (5) select comparative measures and calculate the original utility score; (6) place a common utility scale and calculate the standardized utility score; (7) calculate the comprehensive utility score; (8) rank the drugs; and (9) perform a sensitivity analysis. The model was applied to the evaluation of three different inhaled corticosteroids (ICSs) used for asthma management in children (a total of 16 drugs with different dosage forms and strengths or different manufacturers).. By applying the drug analysis model, the 16 ICSs under review were successfully scored and evaluated. Budesonide suspension for inhalation (drug ID number: 7) ranked the highest, with comprehensive utility score of 80.23, followed by fluticasone propionate inhaled aerosol (drug ID number: 16), with a score of 79.59, and budesonide inhalation powder (drug ID number: 6), with a score of 78.98. In the sensitivity analysis, the ranking of the top five and lowest five drugs remains unchanged, suggesting this model is generally robust.. An evidence-based drug evaluation model based on AHP was successfully developed. The model incorporates sufficient utility and flexibility for aiding the decision-making process, and can be a useful tool for the CCES-P.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aerosols; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Decision Support Techniques; Fluticasone; Humans; Powders

To determine the persistence, exacerbations, and use of resources in patients who use inhaler treatment with fluticasone propionate/formoterol (PF/Form) in relation with other combinations of inhaled corticosteroid/long-acting β-adrenergic (ICS/LABA) at fixed doses, for the treatment of asthma in real-life practice.. Observational study conducted by reviewing medical records. The study included subjects ≥18 years of age who started treatment with ICS/LABA and who met certain inclusion/exclusion criteria. The follow-up was carried out for one year. Study groups: a) PF/Form and b) Other-combinations (Other-ICS/LABA).. Persistence, medication possession ratio (MPR), exacerbations, and costs (direct/indirect). The statistical analysis was performed using regression models, with a P<.05.. A total of 3,203 patients were included in the study. By groups: a) FP/Form: 7.0% and b) Other-ICS/LABA: 93.0%. The mean age was 52.2 years, and 60.8% were women. A total of 44.9% of patients had persistent-moderate asthma. Patients under treatment with FP/Form were associated with greater persistence (67.6 vs. 61.2%, P=.043), a higher RPM (80.6 vs. 74.3%, P=.002), and less exacerbations (16.0 vs. 21.9%, P=.021), particularly severe-exacerbations (4.0 vs. 7.7%, P=.043). The mean/unit of the total cost (ANCOVA) was lower in patients under treatment with PF/Form (2,033 vs. € 2,486, P=.012), respectively. The total cost was associated with: Exacerbations (β=0.618), asthma-severity (β=0.214), age (β=0.073), and lack-adherence (RPM: β=-0.031), P<.01.. Patients undergoing treatment with PF/Form were associated with greater adherence to treatment (persistence, RPM), a circumstance that leads to less severe exacerbations and total costs for the national health system. These differences could be due to the pharmacological properties of the drug or other factors not measured.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-Agonists; Adult; Aged; Anti-Asthmatic Agents; Asthma; Delayed-Action Preparations; Drug Combinations; Female; Fluticasone; Follow-Up Studies; Formoterol Fumarate; Glucocorticoids; Humans; Male; Medication Adherence; Middle Aged; National Health Programs; Retrospective Studies; Severity of Illness Index; Young Adult

Topics: Administration, Inhalation; Adolescent; Asthma; Bronchodilator Agents; Child; Child, Preschool; Disease Progression; Dose-Response Relationship, Drug; Fluticasone; Glucocorticoids; Humans; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Self-Management

The maintaining of asthma control is difficult due to high variability in response to therapy among patients. Since matrix metalloproteinase 9 (MMP9) is implicated in inflammation and remodeling of asthmatic airways, it could be associated with adequate response to asthma therapy. The aim of this study was to investigate whether variants in 3' end of the MMP9 gene are associated with clinical phenotype and responsiveness to treatment in children with asthma.. The study included 127 asthmatic children from Slovenia. Variants in the 3' end of the MMP9 gene were analyzed by direct DNA sequencing and the obtained results were correlated with clinical parameters.. Two variants were detected, rs13925 and rs20544. For the variant rs20544, statistically significant difference in airway hyperresponsiveness (p = 0.011) and asthma control (p = 0.049) between genotypes was found. Patients with TT genotype had lower airway sensitivity, and after 12 months of treatment showed significant improvement in Asthma Control Test (ACT) scores compared to CC and CT genotype. For the variant rs13925, the association with lung function was observed. The carriers of A allele showed noticeable improvement of lung function after the first 6 months of treatment in comparison to the carriers of G allele (p = 0.046).. The main finding of our study is the association of MMP9 genotypes rs20544 TT and rs13925 AA and AG with better asthma control, and indirectly better response to treatment. Based on these results, MMP9 deserves further research as a potential predictive biomarker for asthma.

Topics: 3' Untranslated Regions; Acetates; Adolescent; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Cyclopropanes; Female; Fluticasone; Forced Expiratory Volume; Genetic Variation; Humans; Male; Matrix Metalloproteinase 9; Nitric Oxide; Prognosis; Quinolines; Respiration; Respiratory Hypersensitivity; Sequence Analysis, DNA; Slovenia; Sulfides; Treatment Outcome; Vital Capacity

Topics: Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Fluticasone; Glucocorticoids; Humans

Studies have linked the use of inhaled corticosteroids (ICSs) to excess pneumonia risk in chronic obstructive pulmonary disease patients. The risk in asthma patients remains unclear. The objective of the present study was to examine the risk of pneumonia with ICSs in asthma patients aged 12-35 years.. We formed a cohort of asthma patients treated from 1990 to 2007 using Quebec health insurance databases. Subjects were considered currently exposed if they had had an ICS dispensed within the 60 days prior to their pneumonia index event or matched person-moment. Secondary analyses investigated the risk of pneumonia according to ICS dose and type. Rate ratios (RRs) and rate differences (RDs) were both estimated through a quasi-cohort approach.. The cohort included 152 412 subjects, of whom 1928 had a pneumonia event during follow-up. There was an increased risk of pneumonia associated with current use of ICSs [RR 1.83; 95% confidence interval (CI) 1.57, 2.14] or an excess risk of 1.44 cases per 1000 person-years (RD 1.44; 95% CI 1.03, 1.85). There was an excess pneumonia risk with low doses (RR 1.60; 95% CI 1.06, 2.45), moderate doses (RR 1.53; 95% CI 1.12, 2.08) and high doses (RR 1.96; 95% CI 1.64, 2.34) of ICSs, and with budesonide (RR 2.67; 95% CI 2.05, 3.49) and fluticasone (RR 1.93; 95% CI 1.58, 2.36), specifically relative to no use. When accounting for potential protopathic bias, the risk with current use of ICSs was attenuated (RR 1.48; 95% CI 1.22, 1.78).. ICS use in asthma patients appears to be associated with an increased risk of pneumonia and is present for both budesonide and fluticasone.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Cohort Studies; Databases, Factual; Female; Fluticasone; Humans; Male; Pneumonia; Quebec; Young Adult

To characterise a biorelevant simulated lung fluid (SLF) based on the composition of human respiratory tract lining fluid. SLF was compared to other media which have been utilized as lung fluid simulants in terms of fluid structure, biocompatibility and performance in inhalation biopharmaceutical assays.. The structure of SLF was investigated using cryo-transmission electron microscopy, photon correlation spectroscopy and Langmuir isotherms. Biocompatibility with A549 alveolar epithelial cells was determined by MTT assay, morphometric observations and transcriptomic analysis. Biopharmaceutical applicability was evaluated by measuring the solubility and dissolution of beclomethasone dipropionate (BDP) and fluticasone propionate (FP), in SLF.. SLF exhibited a colloidal structure, possessing vesicles similar in nature to those found in lung fluid extracts. No adverse effect on A549 cells was apparent after exposure to the SLF for 24 h, although some metabolic changes were identified consistent with the change of culture medium to a more lung-like composition. The solubility and dissolution of BDP and FP in SLF were enhanced compared to Gamble's solution.. The SLF reported herein constitutes a biorelevant synthetic simulant which is suitable to study biopharmaceutical properties of inhalation medicines such as those being proposed for an inhaled biopharmaceutics classification system.

Topics: A549 Cells; Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Beclomethasone; Body Fluids; Fluticasone; Humans; Lung; Solubility

Topics: Albuterol; Animals; Asthma; Bronchodilator Agents; Child; Diagnosis, Differential; Fluticasone; Guinea Pigs; Humans; Hypersensitivity; Immunoglobulin E; Male; Respiratory Sounds; Rhinitis, Allergic; Spirometry

To predict the cellular-level epithelial absorbed dose from deposited inhaled corticosteroid (ICS) particles in a model of an expanding and contracting small airway segment for different particle forms.. A computational fluid dynamics (CFD)-based model of drug dissolution, absorption and clearance occurring in the surface liquid of a representative small airway generation (G13) was developed and used to evaluate epithelial dose for the same deposited drug mass of conventional microparticles, nanoaggregates and a true nanoaerosol. The ICS medications considered were budesonide (BD) and fluticasone propionate (FP). Within G13, total epithelial absorption efficiency (AE) and dose uniformity (microdosimetry) were evaluated.. Conventional microparticles resulted in very poor AE of FP (0.37%) and highly nonuniform epithelial absorption, such that <5% of cells received drug. Nanoaggregates improved AE of FP by a factor of 57-fold and improved dose delivery to reach approximately 40% of epithelial cells. True nanoaerosol resulted in near 100% AE for both drugs and more uniform drug delivery to all cells.. Current ICS therapies are absorbed by respiratory epithelial cells in a highly nonuniform manner that may partially explain poor clinical performance in the small airways. Both nanoaggregates and nanoaerosols can significantly improve ICS absorption efficiency and uniformity.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aerosols; Anti-Asthmatic Agents; Asthma; Biological Transport; Bronchodilator Agents; Budesonide; Computational Biology; Drug Delivery Systems; Drug Liberation; Fluticasone; Humans; Molecular Dynamics Simulation; Nanoparticles; Respiratory Therapy; Surface Properties; Trachea

Asthma has a substantial impact on quality of life and health care resources. The identification of a more cost-effective, yet equally efficacious, treatment could positively influence the economic burden of this disease. Fluticasone propionate/Formoterol (FP/FOR) may be as effective as Fluticasone Salmeterol (FP/SAL). We evaluated non-inferiority of asthma control in terms of the proportion of patients free from exacerbations, and conducted a cost impact analysis.. This historical, matched cohort database study evaluated two treatment groups in the Optimum Patient Care Research Database in the UK: 1) an FP/FOR cohort of patients initiating treatment with FP/FOR or changing from FP/SAL to FP/FOR and; 2) an FP/SAL cohort comprising patients initiating, or remaining on FP/SAL pMDI combination therapy. The main outcome evaluated non-inferiority of effectiveness (defined as prevention of severe exacerbations, lower limit of the 95% confidence interval (CI) of the mean difference between groups in patient proportions with no exacerbations is -3.5% or higher) in patients treated with FP/FOR versus FP/SAL.. After matching 1:3, we studied a total of 2472 patients: 618 in the FP/FOR cohort (174 patients initiated on FP/FOR and 444 patients changed to FP/FOR) and 1854 in the FP/SAL cohort (522 patients initiated FP/SAL and 1332 continued FP/SAL). The percentage of patients prescribed FP/FOR met non-inferiority as the adjusted mean difference in proportion of no severe exacerbations (95%CI) was 0.008 (-0.032, 0.047) between the two cohorts. No other significant differences were observed except acute respiratory event rates, which were lower for patients prescribed FP/FOR (rate ratio [RR] 0.82, 95% CI 0.71, 0.94).. Changing to, or initiating FP/FOR combination therapy, is associated with a non-inferior proportion of patients who are severe exacerbation-free at a lower average annual cost compared with continuing or initiating treatment with FP/SAL.

Topics: Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Cohort Studies; Cost-Benefit Analysis; Drug Combinations; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Humans; Male; Middle Aged; Patient Acceptance of Health Care; Quality of Life; Treatment Outcome; United Kingdom

Topics: Asthma; Drug Interactions; Fluticasone; Humans

Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Fluticasone; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System

Asthmatic airways are inflamed and undergo remodelling. Inhaled corticosteroids and long-acting β2-agonist combinations are more effective than inhaled corticosteroid monotherapy in controlling disease exacerbations, but their effect on airway remodelling and inflammation remains ill-defined. This study evaluates the contribution of inhaled fluticasone and salmeterol, alone or combined, to the reversal of bronchial remodelling and inflammation. Severely asthmatic horses (6 horses/group) were treated with fluticasone, salmeterol, fluticasone/salmeterol, or with antigen avoidance for 12 weeks. Lung function, central and peripheral airway remodelling, and bronchoalveolar inflammation were assessed. Fluticasone/salmeterol and fluticasone monotherapy decreased peripheral airway smooth muscle remodelling after 12 weeks (p = 0.007 and p = 0.02, respectively). On average, a 30% decrease was observed with both treatments. In central airways, fluticasone/salmeterol reversed extracellular matrix remodelling after 12 weeks, both within the lamina propria (decreased thickness, p = 0.005) and within the smooth muscle layer (p = 0.004). Only fluticasone/salmeterol decreased bronchoalveolar neutrophilia (p = 0.03) to the same extent as antigen avoidance already after 8 weeks. In conclusion, this study shows that fluticasone/salmeterol combination decreases extracellular matrix remodelling in central airways and intraluminal neutrophilia. Fluticasone/salmeterol and fluticasone monotherapy equally reverse peripheral airway smooth muscle remodelling.

Topics: Adolescent; Airway Remodeling; Animals; Antigens; Asthma; Bronchodilator Agents; Child; Disease Progression; Extracellular Matrix; Female; Fluticasone; Horses; Humans; Male; Muscle, Smooth; Neutrophil Infiltration; Neutrophils; Salmeterol Xinafoate; Severity of Illness Index; Young Adult

Bronchial epithelial goblet cell metaplasia (GCM) with hyperplasia is a prominent feature of asthma, but the effects of treatment with corticosteroids alone or in combination with a long-acting β. To determine whether corticosteroid alone or in combination with a LABA alters protein and gene expression pathways associated with IL-13-induced goblet cell metaplasia.. We evaluated the effects of fluticasone propionate (FP) and of salmeterol (SM), on the response of well-differentiated cultured bronchial epithelial cells to interleukin-13 (IL-13). Outcome measures included gene expression of SPDEF/FOXa2, gene expression and protein production of MUC5AC/MUC5B and morphologic appearance of cultured epithelial cell sheets. We additionally analysed expression of these genes in bronchial epithelial brushings from healthy, steroid-naïve asthmatic and steroid-treated asthmatic subjects. In cultured airway epithelial cells, FP treatment inhibited IL-13-induced suppression of FOXa2 gene expression and up-regulation of SPDEF, alterations in gene and protein measures of MUC5AC and MUC5B and induction of GCM. The addition of SM synergistically modified the effects of FP modestly-only for gel-forming mucin MUC5AC. In bronchial epithelial cells recovered from asthmatic vs healthy human subjects, we found FOXa2 and MUC5B gene expression to be reduced and SPDEF and MUC5AC gene expression to be increased; these alterations were not observed in bronchial epithelial cells recovered after treatment with inhaled corticosteroids.. Corticosteroid treatment inhibits IL-13-induced GCM of the airways in asthma, possibly through its effects on SPDEF and FOXa2 regulation of mucin gene expression. These effects are modestly augmented by the addition of a long-acting ß-agonist. As we found evidence for drug treatment counteracting the effects of IL-13 on the epithelium, we conclude that further exploration into the mechanisms by which corticosteroids and long-acting β

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Biomarkers; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Fluticasone; Gene Expression Regulation; Goblet Cells; Hepatocyte Nuclear Factor 3-beta; Humans; Interleukin-13; Metaplasia; Mucins; Proto-Oncogene Proteins c-ets; Respiratory Mucosa; Salmeterol Xinafoate

In FP/FORM-treated patients aged ≥12 years, asthma control (Asthma Control Test™ [ACT]), incidence of severe exacerbations, lung function, quality of life (asthma quality of life questionnaire [AQLQ]) and adverse events (AEs) were assessed over one year.. Almost 40% (n = 555) of the full analysis population (N = 1410) were receiving ICS/LABA therapy prior to enrolment; 69.8% completed the study. Asthma control (mean ACT ± standard deviation) improved from 16.3 ± 5.0 at baseline to 19.8 ± 4.5 at study end. ACT scores were significantly (p < 0.0001) higher than baseline at all observation timepoints, including the first assessment at 4-6 weeks. The percentage of patients with asthma control increased (baseline: 30.9%; study end: 62.4%), and the percentage of patients with ≥1 severe asthma exacerbation decreased (12 months before: 35.8%; during study: 5.9%). Lung function (forced expiratory volume in one second, peak expiratory flow) improved from baseline to each observation timepoint (p < 0.0001 for all). Improvement in asthma status was accompanied by ameliorated quality of life: AQLQ scores improved significantly from baseline to all observation timepoints (p < 0.0001 for all). AEs accorded with the summary of product characteristics. After study completion, 70% of patients continued FP/FORM treatment.. In this one-year study, FP/FORM treatment was associated with clinically relevant improvements in asthma status in a diverse population of patients under real-life conditions.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Disease Progression; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Metered Dose Inhalers; Middle Aged; Prospective Studies; Quality of Life; Treatment Outcome; Young Adult

Ritonavir is a powerful inhibitor of the cytochrome P450 3A4 (CYP3A4) isoenzyme. It is used as a pharmaceutical enhancer in the management of HIV-positive patients. However, when co-administered with other drugs that are metabolised via the CYP3A4 pathway, ritonavir can potentially cause serious drug-drug interactions. Inhaled fluticasone propionate, which is used to treat asthma and chronic obstructive airway disease, is particularly prone to such interactions due to its physiological attributes. We report a HIV-positive 48-year-old male patient who presented to Al Nahdha Hospital, Muscat, Oman, in 2012 with weight loss, generalised weakness and fatigue and diagnosed with secondary adrenal insufficiency as a result of concomitant ritonavir and inhaled fluticasone.

Topics: Administration, Inhalation; Adrenal Insufficiency; Asthma; Bronchodilator Agents; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Male; Middle Aged; Oman; Ritonavir

Use of a spacer device to optimize the delivery of fluticasone to infants with asthma is an important issue and clinicians require guidance around the choice of device. This in vitro study characterizes the particle size and the fluticasone delivery via 9 spacers.. We used an in vitro infant nasal cast with two different inspiratory flow rates (50 and 100mL/s). Fluticasone particle size in the aerosol was evaluated by laser diffractometry and tracheal deposition by spectrophotometric assay.. Significant differences in particle size were observed between the 9 spacers (similar D50 but D90 from 5.65±0.65 to 8.80±1.35μm). A 75 % or higher respirable fraction was obtained for only 5 spacers. The 50mL/s flow rate lead to the best drug delivery. At this flow, OptiChamber. This study shows a wide variation of drug delivery between the 9 spacers studied. We demonstrate that a low inspiratory flow and a spacer showing antistatic properties facilitate drug delivery.

Topics: Aerosols; Anti-Asthmatic Agents; Asthma; Dose-Response Relationship, Drug; Equipment Design; Fluticasone; Humans; Infant; Metered Dose Inhalers; Nebulizers and Vaporizers; Trachea

Acute worsening of asthma symptoms (exacerbation) is predominantly triggered by respiratory viruses, with influenza causing the most severe exacerbations. The lack of an adequate animal model hampers mechanistic insight and the development of new therapeutics.. We developed and characterized a robust, consistent, and reproducible mouse model of severe exacerbation of chronic allergic asthma.. Chronic allergic airway inflammation was induced following a house dust mite (HDM) sensitization protocol. HDM-sensitized mice and controls were infected with influenza virus A/X31 H3N2 and either or not treated with inhaled fluticasone propionate (FP), systemic corticosteroids (Pred), or anti-IL-5. Mice were killed at different time points after infection: Cellular accumulation and cytokines levels in the airways, PenH as a measure of airway hyper-responsiveness (AHR), and lung histology and viral replication were assessed.. Infection with low-dose A/X31 H3N2 led to prolonged deterioration of lung function, aggravated mucus production, peri-vascular, peri-bronchial, and allergic inflammation that was unresponsive to inhaled corticosteroids, but responsive to systemic corticosteroids. The exacerbation was preceded at 14 h after virus exposure by a marked innate, but no Th2 and Th1 response subsequently followed by enhanced numbers of eosinophils, neutrophils, dendritic, and T cells into the lung lumen, parenchyma, and draining lymph nodes in HDM-sensitized mice. Anti-IL-5 treatment attenuated eosinophils and prevented the X31-induced exacerbation.. Together, these findings indicate that an early innate response that involves eosinophils underlies the exacerbation. This model recapitulates all major features of severe asthma exacerbations and can serve to discern driving mechanisms and promote the development of novel therapeutics.

Topics: Allergens; Amphiregulin; Animals; Anti-Asthmatic Agents; Antibodies, Monoclonal; Asthma; Biopsy; Cytokines; Disease Models, Animal; Disease Progression; Drug Tolerance; Eosinophils; Fluticasone; Immunity, Innate; Immunization; Influenza A virus; Interleukin-5; Male; Mice; Orthomyxoviridae Infections; Pyroglyphidae; Steroids; Viral Load

It has been hypothesized that some patients with chest tightness of unknown origin can be successfully treated with a bronchodilator and that they should be diagnosed with chest pain variant asthma. We conducted a prospective study to characterize newly diagnosed patients with chest tightness relieved with bronchodilator use and without characteristic bronchial asthma attacks.. Eleven patients were registered following recurrent positive responses of chest tightness to inhalation of a ß. For the patients with chest tightness relieved with bronchodilator use, the bronchial biopsy specimens exhibited significant increases in lymphocyte and macrophage infiltration (p < 0.05) and no significant increase in eosinophils (p = 0.2918) compared with the control subjects. The bronchial responsiveness to methacholine was increased in two of the patients with chest tightness, and it was not increased in seven; in addition, increased percentages of eosinophils were detected in bronchial lavage fluid (5% or more) from two patients, but no increase was detected in eight patients.. We suspect that the chest tightness was induced by airway constriction in these patients, but further study is necessary to validate this hypothesis. We propose that the chest tightness relieved with bronchodilator use was attributed to airway constriction resulting from inflammation with lymphocytes and macrophages and/or that the chest tightness was directly attributed to airway inflammation. This clinical trial is registered at www.umin.ac.jp (UMIN13994 and UMIN 16741).

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Airway Obstruction; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Bronchoscopy; Chest Pain; Chronic Disease; Eosinophils; Female; Fluticasone; Humans; Lymphocytes; Macrophages; Male; Middle Aged; Procaterol; Prospective Studies; Respiratory Function Tests

Roflumilast is approved as an add-on therapy for chronic obstructive pulmonary disease. The inflammation in chronic obstructive pulmonary disease is mainly neutrophilic, while in asthma it is mainly eosinophilic, studies addressing role of roflumilast in eosinophilic inflammation are recommended. Also in severe asthma, the dominant inflammatory cells are neutrophils. Thus, roflumilast has a potential off-label use in the treatment of asthma. This study was designed to evaluate the effects of co-inhalation of roflumilast and fluticasone compared to that of formoterol and fluticasone in ovalbumin-sensitized and-challenged BALB/c mice. Besides normal control group, the ovalbumin-asthmatic mice were randomly divided into seven groups (n = 8): positive control, vehicle-treated, and five drug-treated groups. Treatments (µg/kg) were given as 15 min-inhalation once/day for five days as follows: roflumilast (500), formoterol (50), fluticasone (1000), roflumilast + fluticasone (500 + 1000), and formoterol + fluticasone (50 + 1000). Penh values were measured in conscious unrestrained mice using the single-chamber whole-body plethysmography. Airway hyperreactivity to inhaled methacholine was evaluated. Bronchoalveolar lavage fluid was used for the measurements of levels of IL-4, IL-5, TNF-α, OVA-specific IgE, and total and differential white cells. Lung sections were stained with hematoxylin and eosin and periodic acid-Schiff. The asthmatic mice showed significant increases in airway hyperreactivity which were significantly reversed by the combination treatments. The asthmatic mice showed significant increases in levels of IL-4, IL-5, TNF-α, ovalbumin-specific IgE, and total and differential white cells in bronchoalveolar lavage fluid. All treatments (except formoterol) significantly reversed these changes mainly with roflumilast + fluticasone. The asthmatic mice showed severe inflammatory infiltration and goblet cell hyperplasia which were maximally reversed by roflumilast + fluticasone, while minimally reversed by formoterol. In conclusion, co-inhalation of roflumilast + fluticasone more significantly improved inflammation and histopathological changes than co-inhalation of formoterol + fluticasone in ovalumin-asthmatic mice. Further studies are needed to help confirm the potential off-label add-on use of roflumilast in typical and atypical asthma and asthma-chronic obstructive pulmonary disease overlap syndrome. Impact statement Roflumilast, a selective phosphodie

Topics: Administration, Inhalation; Aminopyridines; Animals; Anti-Asthmatic Agents; Asthma; Benzamides; Bronchoalveolar Lavage Fluid; Cyclopropanes; Disease Models, Animal; Drug Therapy, Combination; Female; Fluticasone; Formoterol Fumarate; Immunoglobulin E; Interleukin-4; Interleukin-5; Mice; Mice, Inbred BALB C; Tumor Necrosis Factor-alpha

Topics: Adrenal Insufficiency; Aged; Antifungal Agents; Asthma; Bronchodilator Agents; Drug Interactions; Fatigue; Female; Fluid Therapy; Fluticasone; Glucocorticoids; Humans; Itraconazole; Pulmonary Aspergillosis; Treatment Outcome

Here we investigated the relationship between local bacterial colonization and anti-bacterial immune responses in pre-school asthmatic and control children within the EU-wide study PreDicta. In this cohort of pre-school asthmatic children, nasopharyngeal colonization with Gram-negative bacteria such as Haemophilus influenzae and Moraxella catarrhalis was found to be associated with the highest interferon beta (IFNβ) and IL-33 levels in the nasal pharyngeal fluids (NPF). IL33R-ST2 was found induced in the blood of asthmatic children with additional Gram + bacteria in the nasopharynx (Gr+/-). Furthermore, asthmatic children had more episodes of infection that required antibiotic therapy than the control group. Treatment with antibiotics associated with reduced ST2 in blood cells of both asthmatic and control children and reduced IL-33 levels in the airways of asthmatic children. In the absence of Staphylococcus (S.) aureus in NPF, antibiotic therapy associated with decreased IL-33 levels in the NPF and lower ST2 values in the blood of control children but not of asthmatic children. These data suggest that, in asthmatic children, Gram- bacteria, which persist after antibiotic therapy, contributes to IL-33 locally and associated with Gr + bacteria colonization in the airways, inhibited IFN-β and in the absence of Staphylococcus (S.) aureus, induced ST2 bearing cells in their blood.

Topics: Anti-Bacterial Agents; Asthma; Bronchodilator Agents; Case-Control Studies; Child; Child, Preschool; Female; Fluticasone; Gene Expression Regulation; Haemophilus Infections; Haemophilus influenzae; Humans; Interferon-beta; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Male; Moraxella catarrhalis; Moraxellaceae Infections; Nasopharynx; Respiratory Function Tests; Salmeterol Xinafoate; Staphylococcal Infections; Staphylococcus aureus

The asthmatic patient's respiratory tract deposition of HFA fluticasone (Flovent HFA(™)) has not been established. There is a known large particle size difference with another commercial inhaled HFA steroid (QVAR(™)). This study compared the 2D and 3D respiratory tract deposition of each inhaled steroid.. This study was an open label, crossover study in eight patients diagnosed with asthma. The regional respiratory and oropharyngeal deposition of the two steroids were compared and contrasted using planar and SPECT imaging following delivery of the (99m)Tc-radiolabeled drug in each product. The SPECT images were merged with computed tomography images to quantify regional deposition within the patients.. Two-dimensional (2D) planar images indicated that 24% of the Flovent HFA dose and 55% of the QVAR dose deposited in the lungs. 2D oropharyngeal deposition indicated that 75% of the Flovent HFA dose was deposited in the oropharynx, while 42% of the QVAR dose deposited in the oropharynx. Three-dimensional (3D) SPECT data indicated that 22% of the Flovent HFA dose and 53% of the QVAR dose deposited in the lungs. 3D oropharyngeal and gut deposition indicated 78% of the Flovent HFA dose was deposited in the oropharynx, while 47% of the QVAR dose deposited in the oropharynx. The increased lung deposition and decreased oropharynx deposition for both 2D and 3D image data of QVAR were statistically different from Flovent HFA.. QVAR exhibited a significant increase in lung delivery compared to Flovent HFA. Conversely, QVAR delivered a significantly lower dose to the oropharynx than Flovent HFA. The findings were presumed to be driven by the smaller particle size of QVAR (0.7 microns MMAD) compared with Flovent HFA (2.0 microns MMAD).

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Aerosols; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Cross-Over Studies; Drug Compounding; Fluticasone; Humans; Hydrocarbons, Fluorinated; Lung; Male; Metered Dose Inhalers; Middle Aged; Multimodal Imaging; Oropharynx; Particle Size; Radiographic Image Interpretation, Computer-Assisted; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Young Adult

Few instruments exist to ascertain the severity of a preschool-aged child's asthma exacerbations managed at home.. We sought to develop and validate a functional status instrument to assess asthma exacerbation severity in preschoolers.. The parent-completed Asthma Flare-up Diary for Young Children (ADYC), which was developed systematically, comprises 17 items, each scored from 1 (best) to 7 (worst). The ADYC was completed daily from the onset of an upper respiratory tract infection (URTI) until asthma symptom resolution; the cumulative daily score was reported. The ADYC was examined for key psychometric properties in a randomized placebo-controlled trial of pre-emptive high-dose fluticasone in preschoolers with URTI-induced asthma.. In 121 children aged 2.7 ± 1.1 years (59.5% male), the ADYC's internal consistency (Cronbach α = .97), feasibility (97% completion), and test-retest reliability (r = 0.71; 95% CI, 0.59-0.80) were demonstrated. The ADYC was responsive to change between 2 consecutive days (Guyatt statistic = 0.77) with a minimal important difference of 0.22 (0.17-0.27). Of 871 episodes, the cumulative ADYC score was significantly higher during exacerbations than during URTIs (mean difference [MD], 7.6; 95% CI, 6.4-8.9) and for exacerbations with an acute-care visit (MD, 9.1; 95% CI, 7.6-10.7), systemic corticosteroids (MD, 10.1; 95% CI, 8.3-12.0), and hospitalization (MD, 6.8; 95% CI, 2.9-10.7) versus those without. In children receiving fluticasone, the ADYC score was significantly lower versus that in the placebo group (MD, 5.1; 95% CI, 1.8-8.3).. The 17-item ADYC proved feasible, responsive to day-to-day changes, and discriminative across exacerbations of different severities. In a trial testing effective therapy in preschoolers, it identified a significant reduction in asthma exacerbation severity.

Topics: Anti-Asthmatic Agents; Asthma; Child, Preschool; Disease Progression; Female; Fluticasone; Health Records, Personal; Humans; Infant; Male; Risk Factors; Severity of Illness Index

Human lung mast cells (HLMCs) play a central role in asthma pathogenesis through their relocation to the airway smooth muscle (ASM) bundles. β2 adrenoceptor (β2-AR)-agonists are used to relieve bronchoconstriction in asthma, but may reduce asthma control, particularly when used as monotherapy. We hypothesized that HLMC and human ASM cell (HASMC) responsiveness to β2-AR agonists would be attenuated when HLMCs are in contact with HASMCs. Cells were cultured in the presence of the short-acting β2-agonist albuterol, and the long-acting β2-agonists formoterol and olodaterol. Constitutive and FcεRI-dependent HLMC histamine release, HASMC contraction, and β2-AR phosphorylation at Tyr(350) were assessed. Constitutive HLMC histamine release was increased in HLMC-HASMC coculture and this was enhanced by β2-AR agonists. Inhibition of FcεRI-dependent HLMC mediator release by β2-agonists was greatly reduced in HLMC-HASMC coculture. These effects were reversed by neutralization of stem cell factor (SCF) or cell adhesion molecule 1 (CADM1). β2-AR agonists did not prevent HASMC contraction when HLMCs were present, but this was reversed by fluticasone. β2-AR phosphorylation at Tyr(350) occurred within 5 min in both HLMCs and HASMCs when the cells were cocultured, and was inhibited by neutralizing SCF or CADM1. HLMC interactions with HASMCs via CADM1 and Kit inhibit the potentially beneficial effects of β2-AR agonists on these cells via phosphorylation of the β2-AR. These results may explain the potentially adverse effects of β2-ARs agonists when used for asthma therapy. Targeting SCF and CADM1 may enhance β2-AR efficacy, particularly in corticosteroid-resistant patients.

Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Asthma; Benzoxazines; Cell Adhesion Molecule-1; Cell Adhesion Molecules; Cells, Cultured; Coculture Techniques; Fluticasone; Formoterol Fumarate; Histamine; Histamine Release; Humans; Immunoglobulins; Lung; Mast Cells; Muscle, Smooth; Myocytes, Smooth Muscle; Phosphorylation; Receptors, Adrenergic, beta-2; Receptors, IgE; Stem Cell Factor

Inhaled corticosteroids (ICS) reduce growth during the first year of treatment, but this growth suppressing effect does not continue during further treatment. Decreasing adherence may play a role in explaining this. The aim of this study was to examine the relationship between cumulative real exposure (with objectively assessed adherence) to ICS and height growth in children with asthma.. We investigated 99 prepubertal children with asthma, 2-13 years of age, who had been using ICS in guideline-recommended dosages for ≥3 months, and continued to do so during 1-year follow-up. ICS adherence was assessed by electronic monitoring devices, allowing calculation of true cumulative exposure to ICS. We analysed the relationship between cumulative ICS dose and height growth velocity (assessed as change in height SD score) over 1 year.. Median (IQR) adherence over 1 year was 84 (68-92) %. Mean cumulative fluticasone dose was 64.6 (SD, 27.8) mg, reflecting a daily dose of 167 (SD, 7) µg. The negative correlation between cumulative ICS dose and height growth velocity (r=-0.266; p=0.008) became non-significant after adjustment for age and sex in a multiple regression model (adjusted r=-0.188; p=0.066).. One year of ICS treatment in guideline-recommended dosages with high adherence did not result in significant or relevant growth suppression. Unaffected growth can be maintained for at least 1 year in children with asthma during ICS treatment with high adherence.

Topics: Administration, Inhalation; Adolescent; Anthropometry; Asthma; Body Height; Bronchodilator Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Fluticasone; Glucocorticoids; Growth Disorders; Humans; Male; Medication Adherence; Practice Guidelines as Topic

Inhaled corticosteroids (ICSs) are currently used to prevent and treat asthma and recurrent wheezing attacks in children. Fluticasone propionate (FP) is one of the most commonly prescribed ICSs because it is considered effective and well tolerated.. A male infant of approximately 1 year of age, who was born to parents without relevant clinical problems or family histories including diabetes, was brought to our attention for recurrent wheezing. When he was approximately 2 years old, a regular daily inhaled treatment with FP given using a spacer was prescribed. With this therapy, the child obtained good control of his symptoms with no further recurrences, but after approximately 2 months of treatment he was admitted to the emergency room because he was whining and agitated and exhibited increased diuresis and water intake. Laboratory tests revealed hyperglycaemia (181 mg/dL), mild glycosuria, blood alkalosis (pH 7.49), a bicarbonate level of 31 mmol/L, a pCO2 level of 39 mmHg, a serum sodium level of 135 mEq/L and a serum potassium level of 3.5 mEq/L. The parents confirmed that the recommended dose of FP had been administered with no increase in the amount of drug. The child was immediately treated with endovenous infusion of physiological saline for 24 h, and his glycaemic levels as well as venous blood gas analysis returned to normal, with an absence of glucose in the urine. Oral glucose tolerance test results and glycated haemoglobin levels were normal. Monitoring of blood glucose levels before and after meals for three consecutive days did not reveal any further increase above normal levels. He was discharged with a diagnosis of transient symptomatic hyperglycaemia during ICS therapy and the suggestion to replace his inhaled FP therapy with oral montelukast. Montelukast was continued for 6 months; during this time, the child did not present any other hyperglycaemia episodes.. Although there is no evidence of causation, this case report represents an interesting and unusual description of paediatric transient symptomatic hyperglycaemia after treatment with inhaled FP and highlights the importance of considering this potential adverse event and the necessity of informing parents of the possible clinically relevant risks associated with this drug.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Asthma; Child, Preschool; Fluticasone; Humans; Hyperglycemia; Male; Recurrence; Respiratory Sounds

Topics: Asthma; Bronchodilator Agents; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Male

Genetic associations of the response to inhaled corticosteroids (ICSs) during an asthma exacerbation are unknown.. To evaluate the role of genetic variants in the therapeutic response to high-dose ICS in children with moderate-to-severe asthma exacerbations.. Eighty-two children (56 boys/26 girls, mean age 9.6 ± 3.2 years) with moderate-severe asthma exacerbation were genotyped for eight single-nucleotide polymorphisms that were a priori associated with ICS response in chronic asthma treatment: glucocorticosteroid receptor (NR3C1) rs41423247; corticotrophin-releasing hormone receptor1 (CRHR1) rs242939, rs242941, and rs1876828; T-box 21 (TBX21) rs2240017; glucocorticoid-induced transcript 1 (GLCCl1); and T gene rs3099266 and rs2305089. Children were treated with a single high-dose (4000 μg) fluticasone propionate given by a nebulizer followed by 1000 μg/day of inhaled fluticasone propionate for 6 days. Primary outcome measure was the improvement in FEV1 at 4 h.. Mean FEV1 was 71.7 ± 14.2% at presentation. Overall, fluticasone treatment resulted in a significant improvement in asthma score and FEV1 (p < 0.0001 for both). Children with the GG genotype at NR3C1 rs41423247 (n = 26) had a higher improvement in FEV1 [24.2% (interquartile range 11.5-36.3)] compared to those with CG+CC (n = 19), [7.9% (interquartile range 6.1-24.6) (p = 0.006)].. Homozygosity for the G allele at rs41423247 of the glucocorticosteroid receptor (NR3C1) gene is associated with a higher improvement in FEV1 at 4 h in children with moderate-to-severe asthma exacerbation treated with high-dose ICS. This observation may have important clinical implications especially for children who use systemic steroids frequently for recurrent asthma exacerbations.

Topics: Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Asthma; Biomarkers, Pharmacological; Child; Female; Fluticasone; Gene Frequency; Genetic Association Studies; Genotype; Humans; Male; Receptors, Glucocorticoid; Treatment Outcome

A primary goal of asthma management is the reduction of exacerbation risk. We assessed the occurrence of oral corticosteroid-requiring exacerbations (OCS exacerbations) with long-term fluticasone/formoterol therapy, and compared it with the occurrence of similar events reported with other inhaled corticosteroid/long acting β2-agonist (ICS/LABA) combinations.. The occurrence of OCS exacerbations was assessed in two open-label trials of fixed-dose fluticasone/formoterol administered for between 26 to 60 weeks in adults and adolescents with asthma. The incidence of OCS exacerbations with fluticasone/formoterol was compared with those reported in three recent Cochrane meta-analyses of other ICS/LABAs.. The pooled incidence of OCS exacerbations with long-term fluticasone/formoterol was 2.1% (95% CI: 1.1, 3.2%, n/N = 16/752). In only two of the nineteen treatment arms summarized by Cochrane did OCS exacerbation incidence approximate that seen in the two fluticasone/formoterol trials (single-inhaler fluticasone/salmeterol [2.9%]; separate inhaler budesonide, beclometasone, or flunisolide plus formoterol [3.4%]). In Lasserson's review the pooled incidence of OCS exacerbations for single-inhaler combinations was 9.5% (95% CI: 8.4, 10.6%; n/N = 239/2516) for fluticasone/salmeterol, and 10.6% (95% CI: 9.3, 11.8%; n/N = 257/2433) for budesonide/formoterol. In Ducharme's and Chauhan's meta-analyses (primarily incorporating separate inhaler combinations [fluticasone, budesonide, beclometasone, or flunisolide plus salmeterol or formoterol]), the pooled incidences of OCS exacerbations were 16.0% (95% CI: 14.2, 17.8%, n/N = 258/1615) and 16.7% (95% CI: 14.9, 18.5, n/N = 275/1643), respectively.. The incidence of exacerbations in two fixed-dose fluticasone/formoterol studies was low and less than in the majority of comparable published studies involving other ICS/LABA combinations. This difference could not be readily explained by differences in features of the respective studies and may be related to the favorable pharmacological/mechanistic characteristics of the constituent components fluticasone and formoterol compared to other drugs in their respective classes.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Clinical Trials as Topic; Disease Progression; Drug Combinations; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Incidence; Lung; Male; Medication Adherence; Meta-Analysis as Topic; Middle Aged; Severity of Illness Index; Time Factors; Treatment Outcome

Topics: Androstadienes; Asthma; Bronchodilator Agents; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Metered Dose Inhalers; Particle Size

GLCCI1 variations are found to be associated with response to glucocorticoid therapy in non-Hispanic white subjects with asthma. However, there are also other relevant studies that were not consistent with this finding. In this study we aimed to evaluate the association of GLCCI1 variations with asthma susceptibility and inhaled corticosteroid (ICS) response in a Chinese adult Han population.. We genotyped 24 single nucleotide polymorphisms of GLCCI1 in 182 asthmatic patients and 180 healthy controls. Furthermore, we analyzed the association of GLCCI1 variations with ICS response in 30 mild-to-moderate asthmatics.. rs11976862 homozygote mutant genotype GG was nominally associated with increased asthma risk (OR = 2.435, 95% CI: 1.221-4.854, p = 0.01148, p(corr) = 0.0127). Recessive model of rs37972, rs37973 and rs11976862 showed that the rare alleles were correlated with less improvement in FEV1 after fluticasone treatment for 12 weeks (p = 0.004, p = 0.009 and p = 0.039, respectively). The GLCCI1 mRNA expression level decreased obviously in asthmatics than in healthy controls (0.037663 ± 0.0216833 vs. 0.046352 ± 0.0235812, p = 0.000). For asthmatics, GLCCI1 mRNA expression level significantly increased after fluticasone treatment for 12 weeks (0.067641 ± 0.031547 vs. 0.030048 ± 0.014613, p = 0.000). Moreover, changes of GLCCI1 mRNA expression were significantly related with rs37973 and rs11976862 in a recessive model (p = 0.014 and p = 0.033, respectively).. GLCCI1 variations are associated with asthma susceptibility and ICS response in a Chinese Han adult population. GLCCI1 variations may affect ICS response by modulating GLCCI1 expression.

Topics: Administration, Inhalation; Adult; Aged; Asian People; Asthma; Bronchodilator Agents; Case-Control Studies; Disease Susceptibility; Female; Fluticasone; Genetic Association Studies; Genotype; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptors, Glucocorticoid

To assess the reliability of the Medication Adherence Report Scale (MARS-5) for assessing adherence in clinical practice and research.. Prospective cohort study following electronically measured inhaled corticosteroids (ICS) adherence for 1 year in 2-13-year-old children with persistent asthma. The relationship between electronically measured adherence and MARS-5 scores (ranging from 5 to 25) was assessed by Spearman's rank correlation coefficient. A ROC (receiver operating characteristic) curve was performed testing MARS-5 against electronically measured adherence. Sensitivity, specificity, positive and negative likelihood ratios of the closest MARS-5 cut-off values to the top left-hand corner of the ROC curve were calculated.. High MARS scores were obtained (median 24, interquartile range 22-24). Despite a statistically significant correlation between MARS-5 and electronically assessed adherence (Spearman's rho = 0.47; p < 0.0001), there was considerable variation of adherence rates at every MARS-5 score. The area under the ROC curve was 0.7188. A MARS-5 score ≥23 had the best predictive ability for electronically assessed adherence, but positive and negative likelihood ratios were too small to be useful (1.65 and 0.27, respectively).. Self-report using MARS-5 is too inaccurate to be a useful measure of adherence in children with asthma, both in clinical practice and in research.

Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Female; Fluticasone; Humans; Male; Medication Adherence; Prospective Studies; Self Report; Surveys and Questionnaires

Most randomised clinical trials typically exclude a significant proportion of asthma patients, including those at higher risk of adverse events, with comorbidities, obesity, poor inhaler technique and adherence, or smokers. However, these patients might differentially benefit from extrafine-particle inhaled corticosteroids (ICS). This matched cohort, database study, compared the effectiveness of extrafine-particle with fine-particle ICS in a real-life population initiating ICS therapy in the Netherlands.. Data were from the Pharmo Database Network, comprising pharmacy and hospital discharge records, representative of 20 % of the Dutch population. The study population included patients aged 12 - 60, with a General Practice-recorded diagnosis for asthma (International Classification of Primary Care code R96), when available, ≥2 prescriptions for asthma therapy at any time in their recorded history, and receiving first prescription of ICS therapy as either extrafine-particle (ciclesonide or hydrofluoroalkane beclomethasone dipropionate [BDP]) or fine-particle ICS (fluticasone propionate or non-extrafine-particle-BDP). Patients were matched (1:1) on relevant demographic and clinical characteristics over 1-year baseline. Primary outcomes were severe exacerbation rates, risk domain asthma control and overall asthma control during the year following first ICS prescription. Secondary outcomes, treatment stability and being prescribed higher versus lower category of short-acting β2 agonists (SABA) dose, were compared over a 1-year outcome period using conditional logistic regression models.. Following matching, 1399 patients were selected in each treatment cohort (median age: 43 years; males: 34 %). Median (interquartile range) initial ICS doses (fluticasone-equivalents in μg) were 160 (160 - 320) for extrafine-particle versus 500 (250 - 500) for fine-particle ICS (p < 0.001). Following adjustment for residual confounders, matched patients prescribed extrafine-particle ICS had significantly lower rates of exacerbations (adjusted rate ratio [95 % CI], 0.59 [0.47-0.73]), and significantly higher odds of achieving asthma control and treatment stability in the year following initiation than those prescribed fine-particle ICS, and this occurred at lower prescribed doses. Patients prescribed extrafine-particle ICS had lower odds of being prescribed higher doses of SABA (0.50 [0.44-0.57]).. In this historical, matched study, extrafine-particle ICS was associated with better odds of asthma control than fine-particle ICS in patients prescribed their first ICS therapy in the Netherlands. Of importance, this was reached at significantly lower prescribed dose.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Cohort Studies; Databases, Factual; Female; Fluticasone; Humans; Logistic Models; Male; Middle Aged; Netherlands; Particle Size; Pregnenediones; Treatment Outcome

As expected, the vilanterol + fluticasone combination increases the risk of pneumonia in patients with COPD.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Asthma; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Drug Combinations; Fluticasone; Humans; Pulmonary Disease, Chronic Obstructive

Topics: Anti-Asthmatic Agents; Asthma; Drug Combinations; Evidence-Based Medicine; Family Practice; Fluticasone; Humans; Salmeterol Xinafoate; Severity of Illness Index; United States

Inhaled corticosteroids are the most effective treatment currently available for asthma, but their beneficial effect against airway remodeling is limited. The tyrosine kinase inhibitor nilotinib has inhibitory activity against c-kit and the platelet-derived growth factor receptor. We compared the effects of fluticasone and nilotinib on airway remodeling in a chronic asthma model. We also examined whether co-treatment with nilotinib and fluticasone had any synergistic effect in preventing airway remodeling.. We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized female BALB/c-mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated with fluticasone and/or nilotinib intranasally during the OVA challenge.. Mice chronically exposed to OVA developed eosinophilic airway inflammation and showed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Both fluticasone and nilotinib attenuated airway smooth muscle thickening. However, only nilotinib suppressed fibrotic changes, demonstrating inhibition of collagen deposition. Fluticasone reduced pro-inflammatory cells, such as eosinophils, and several cytokines, such as interleukin 4 (IL-4), IL-5, and IL-13, induced by repeated OVA challenges. On the other hand, nilotinib reduced transforming growth factor β1 levels in bronchoalveolar lavage fluid and inhibited fibroblast proliferation significantly.. These results suggest that fluticasone and nilotinib suppressed airway remodeling in this chronic asthma model through anti-inflammatory and anti-fibrotic pathways, respectively.

Topics: Administration, Intranasal; Airway Remodeling; Animals; Anti-Inflammatory Agents; Asthma; Bronchodilator Agents; Cell Line; Cell Proliferation; Chronic Disease; Collagen; Cytokines; Disease Models, Animal; Drug Therapy, Combination; Female; Fluticasone; Inflammation Mediators; Lung; Mice, Inbred BALB C; Muscle, Smooth; Ovalbumin; Protein Kinase Inhibitors; Pulmonary Fibrosis; Pyrimidines; Transforming Growth Factor beta1

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Drug Combinations; Fluticasone; Humans; Salmeterol Xinafoate

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Drug Combinations; Fluticasone; Humans; Salmeterol Xinafoate

Topics: Administration, Inhalation; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Drug Combinations; Fluticasone; Humans; Salmeterol Xinafoate

Topics: Administration, Inhalation; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Drug Combinations; Fluticasone; Humans; Salmeterol Xinafoate

Asthma exacerbations contribute to corticosteroid insensitivity. LPS is ubiquitous in the environment. It causes bronchoconstriction and airway inflammation and may therefore exacerbate allergen responses. This study examined whether LPS and ovalbumin co-administration could exacerbate the airway inflammatory and functional responses to ovalbumin in conscious guinea pigs and whether these exacerbated responses were insensitive to inhaled corticosteroid treatment with fluticasone propionate (FP).. Guinea pigs were sensitized and challenged with ovalbumin and airway function recorded as specific airway conductance by whole body plethysmography. Airway inflammation was measured from lung histology and bronchoalveolar lavage. Airway hyper-reactivity (AHR) to inhaled histamine was examined 24 h after ovalbumin. LPS was inhaled alone or 24 or 48 h before ovalbumin and combined with ovalbumin. FP (0.05-1 mg·mL(-1) ) or vehicle was nebulized for 15 min twice daily for 6 days before ovalbumin or LPS exposure.. Ovalbumin inhalation caused early (EAR) and late asthmatic response (LAR), airway hyper-reactivity to histamine and influx of inflammatory cells into the lungs. LPS 48 h before and co-administered with ovalbumin exacerbated the response with increased length of the EAR, prolonged response to histamine and elevated inflammatory cells. FP 0.5 and 1 mg·mL(-1) reduced the LAR, AHR and cell influx with ovalbumin alone, but was ineffective when guinea pigs were exposed to LPS before and with ovalbumin.. LPS exposure exacerbates airway inflammatory and functional responses to allergen inhalation and decreases corticosteroid sensitivity. Its widespread presence in the environment could contribute to asthma exacerbations and corticosteroid insensitivity in humans.

Topics: Administration, Inhalation; Animals; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Drug Resistance; Fluticasone; Guinea Pigs; Histamine; Inflammation; Lipopolysaccharides; Lung; Male; Ovalbumin; Plethysmography, Whole Body

The airway remodeling in asthma is associated with increased amount of matrix metalloproteinase (MMP)-9. High levels of MMP-9 were found in mucosal biopsies, sputum and in exhaled breath condensates (EBC) of asthma patients. However, there are no data concerning real in vivo activity. Inhaled corticosteroids are effective in asthma control, but it is unclear, whether they only attenuate inflammation, or also protect against progressive remodeling of respiratory tract. Therefore, the aim of the study was to assess the amount and activity of MMP-9 in context of pro-inflammatory cytokines (IL-6, IL-8 and tumor necrosis factor, TNF), measured in EBC of asthma-suffering children, treated with inhaled steroids. The study involved 27 children with asthma, continuously treated with inhaled fluticasone propionate, and 22 healthy controls. In addition to routine clinical screening, the selected cytokines in EBC were analyzed using Ultrasensitive ELISA, whereas activity of MMP-9 was assessed using a novel immunozymography method. Despite chronic treatment with inhaled steroids mean MMP-9/EBC activity in asthma group was significantly higher than in healthy controls. Moreover, high MMP-9/EBC in asthma-suffering children significantly correlated with IgE serum levels. The IL-6 and IL-8 concentration was below the detection limit in all EBC samples. TNF/EBC levels were similar in both, asthma and healthy children. We hypothesize that MMP-9 hyperactivity in asthma may be closely related to high IgE serum levels. Our results suggest that inhaled steroids may be ineffective to prevent asthma-associated airway remodeling. Finally, we emphasize the necessity of further research focused on MMP-9 inhibition in asthma treatment.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Airway Remodeling; Asthma; Breath Tests; Child; Cytokines; Exhalation; Female; Fluticasone; Humans; Immunoglobulin E; Inflammation Mediators; Male; Matrix Metalloproteinase 9; Time Factors

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Age Distribution; Aged; Androstadienes; Asthma; Beclomethasone; Cohort Studies; Fluticasone; Humans; Middle Aged; Smoking; Smoking Cessation; Treatment Outcome; United Kingdom

Little is known about health outcomes in severe asthma reflected by Global Initiative for Asthma steps 4 and 5.. To analyze control, risk, economic, and health resource use (HRU) outcomes associated with treatment escalation to Global Initiative for Asthma steps 4 and 5.. This was a before-vs-after retrospective cohort study of patients (12-75 years old) with asthma newly initiated to omalizumab, high-intensity corticosteroids (HICS; ≥1,000 μg/day of inhaled fluticasone equivalent or oral prednisone), or high-dose inhaled corticosteroid (HDICS; ≥500 to <1,000 μg/day of fluticasone equivalent) using 2002 to 2011 MarketScan data. Poisson regression was used to model HRU outcomes; Tobit regression was used to model medical expenditures.. Of 19,227 patients, 856 initiated omalizumab, 6,926 initiated HICS, and 11,445 initiated HDICS. Use of β-agonist increased for the HDICS and HICS cohorts and decreased for the omalizumab cohort; acute care visits and oral corticosteroid use decreased during follow-up for the HDICS and omalizumab cohorts. Annual health care expenditures, polypharmacy burden, and outpatient visits were high for all cohorts and increased in the follow-up year (baseline to follow-up; general health care expenditures: omalizumab $14,071 to $34,887, HICS $12,030 to $15,557, HDICS $7,570 to $9,826; annual number of asthma prescriptions: omalizumab 11.74 to 19.46, HICS 7.8 to 12.44, HDICS 5.17 to 9.69; outpatient visits: omalizumab 26.79 to 34.06, HICS 18.78 to 21.37, HDICS 15.06 to 16.64).. Omalizumab use was associated with improvements in risk and control accompanied by large increases in expenditures per HRU. Patients on HDICS and HICS showed improvements in risk but worsening control and increased expenditures per HRU. Innovations in disease management and available treatment options are needed to more optimally achieve treatment goals.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Asthma; Bronchodilator Agents; Child; Cohort Studies; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Omalizumab; Retrospective Studies; Treatment Outcome; Young Adult

Preclinical models of human conditions including asthma showed the therapeutic potential of Compound A (CpdA), a dissociated glucocorticoid (GC) receptor (GRα) ligand. Whether CpdA inhibits GC resistance, a central feature of severe asthma, has not been addressed. We investigated whether CpdA modulates cytokine-induced GC resistance in human airway smooth muscle (ASM) cells. Healthy and asthmatic ASM cells were treated with TNF-α/IFN-γ for 24 hours in the presence or absence of CpdA. ELISA and quantitative PCR assays were used to assess the effect of CpdA on chemokine expression. Activation of GRα by CpdA was assessed by quantitative PCR, immunostaining, and receptor antagonism using RU486. An effect of CpdA on the transcription factor interferon regulatory factor 1 (IRF-1) was investigated using immunoblot, immunostaining, and small interfering RNA (siRNA) knockdown. CpdA inhibited production of fluticasone-resistant chemokines CCL5, CX3CL1, and CXCL10 at protein and mRNA levels in both asthmatic and healthy cells. CpdA failed to induce expression of GC-induced Leucine Zipper while transiently inducing mitogen-activated protein kinase phosphatase 1 (MKP-1) at both mRNA and protein levels. CpdA inhibitory action was not associated with GRα nuclear translocation, nor was it prevented by RU486 antagonism. Activation of IRF-1 by TNF-α/IFN-γ was inhibited by CpdA. IRF-1 siRNA knockdown reduced cytokine-induced CCL5 and CX3CL1 production. siRNA MKP-1 prevented the inhibitory effect of CpdA on cytokine-induced CXCL10 production. For the first time, we show that CpdA inhibits the production of GC-resistant chemokines via GRα-independent mechanisms involving the inhibition of IRF-1 and up-regulation of MKP-1. Thus, targeting CpdA-sensitive pathways in ASM cells represents an alternative therapeutic approach to treat GC resistance in asthma.

Topics: Acetates; Adult; Anti-Asthmatic Agents; Asthma; Case-Control Studies; Chemokine CCL5; Chemokine CX3CL1; Chemokine CXCL10; Drug Resistance; Dual Specificity Phosphatase 1; Epithelial Cells; Female; Fluticasone; Gene Expression; Humans; Interferon Regulatory Factor-1; Interferon-gamma; Male; Middle Aged; Mifepristone; Primary Cell Culture; Receptors, Glucocorticoid; Respiratory Mucosa; RNA, Small Interfering; Tumor Necrosis Factor-alpha; Tyramine

The aim of this study was to develop a set of reference genes whose expression is stable and suitable for normalization of target gene expression measured in asthma patients during anti-asthmatic treatment. Real-time qPCR was used to determine expression of 7 candidate reference genes (18S rRNA, ACTB, B2M, GAPDH, POLR2A, RPL13A and RPL32) and 7 target genes in leukocytes from asthma patients before and after treatment with inhaled corticosteroids and leukotriene receptor antagonist. Variance of Cq values was analyzed and stability ranking was determined with geNorm. We further investigated how the different normalization strategies affected the consistency of conclusions if the specific investigated target gene is down-regulated or up-regulated after anti-asthmatic therapy. The top-ranking reference genes determined by geNorm, when samples before and after therapy were analyzed (ACTB, B2M and GAPDH) were different from those (POLR2A and B2M) when only samples before treatment were analyzed. Using only a single reference gene for normalization of 7 target gene expression compared to our strategy, there would be as low as 19% of consistency in conclusions. We suggest the use of the geometric mean of ACTB, B2M and GAPDH for normalization of qPCR data of target genes in pharmacogenomics studies in asthma patients before and after anti-asthmatic therapy, however if gene expression is measured only before anti-asthmatic treatment, we recommend the use of the geometric mean of POLR2A and B2M.

Topics: Adolescent; Androstadienes; Anti-Asthmatic Agents; Asthma; Case-Control Studies; Child; Female; Fluticasone; Gene Expression Profiling; Genes, Essential; Humans; Leukocytes; Male; Real-Time Polymerase Chain Reaction; Reference Standards; Transcriptome; Young Adult

Although the majority of patients with asthma are well controlled by inhaled glucocorticoids (GCs), patients with severe asthma are poorly responsive to GCs. This latter group is responsible for a disproportionate share of health care costs associated with asthma. Recent studies in immune cells have incriminated interferon-γ (IFN-γ) as a possible trigger of GC insensitivity in severe asthma; however, little is known about the role of IFN-γ in modulating GC effects in other clinically relevant nonimmune cells, such as airway epithelial cells. We hypothesized that IFN-γ-induced JAK/STAT-associated signaling pathways in airway epithelial cells are insensitive to GCs and that strategies aimed at inhibiting JAK/STAT pathways can restore steroid responsiveness. Using Western blot analysis we found that all steps of the IFN-γ-induced JAK/STAT signaling pathway were indeed GC insensitive. Transfection of cells with reporter plasmid showed IFN-γ-induced STAT1-dependent gene transcription to be also GC insensitive. Interestingly, real-time PCR analysis showed that IFN-γ-inducible genes (IIGs) were differentially affected by GC, with CXCL10 being GC sensitive and CXCL11 and IFIT2 being GC insensitive. Further investigation showed that the differential sensitivity of IIGs to GC was due to their variable dependency to JAK/STAT vs. NF-κB signaling pathways with GC-sensitive IIGs being more NF-κB dependent and GC-insensitive IIGs being more JAK/STAT dependent. Importantly, transfection of cells with siRNA-STAT1 was able to restore steroid responsiveness of GC-insensitive IIGs. Taken together, our results show the insensitivity of IFN-γ-induced JAK/STAT signaling pathways to GC effects in epithelial cells and also suggest that targeting STAT1 could restore GC responsiveness in patients with severe asthma.

Topics: Active Transport, Cell Nucleus; Aged; Androstadienes; Asthma; Cell Line, Tumor; Epithelial Cells; Female; Fluticasone; Glucocorticoids; Humans; Interferon-gamma; Janus Kinases; Male; Middle Aged; NF-kappa B; Phosphorylation; Protein Processing, Post-Translational; Respiratory Mucosa; Signal Transduction; STAT1 Transcription Factor; Transcription, Genetic

New inhalers propelled by hydrofluoroalkanes (HFAs) have improved plume characteristics: higher fine particle fraction, and warmer plumes with reduced force and velocity. Together, this may avoid reflex interruption of inhalation and improve lung deposition of the inhaled drugs. However, even with HFA-propelled pressurized metered-dose inhalers (pMDIs), there are notable differences in device properties. Here we compared the duration, velocity, force, and temperature of two inhaled corticosteroid/long-acting β2-agonist combination therapies, administered via HFA pMDIs: fluticasone propionate/formoterol 125/5 µg (FP/FORM; flutiform(®)) and fluticasone propionate/salmeterol 125/25 µg (FP/SAL; Seretide(®) Evohaler(®)).. Inhalers were fired into ambient air. Plume duration and velocity were recorded with a high-speed camera and a pulsed laser light source. A copper disc attached to a sensitive load cell measured the plume force at various distances from the device. A thermal imaging video camera recorded impaction temperature in line with the device.. The average plume duration for FP/FORM was longer than that of FP/SAL: 168.3 vs. 114.0 ms, respectively. The mean maximum plume velocities observed at 95 mm (the approximate distance between mouthpiece and throat) was consistently slower for FP/FORM (10.08 m/s) compared to FP/SAL (15.55 m/s). FP/FORM had a slower velocity at the outset, remaining relatively constant before declining steadily over the plume duration. The force of the FP/SAL plume was greater than that of FP/FORM at all distances: maximum force for FP/FORM was 138.2 vs. 278.9 mN for FP/SAL. The minimum impaction temperature was +5.9 °C for FP/FORM and -37.8 °C for FP/SAL; this difference became less pronounced over distance.. There were substantial differences between the plumes of the two pMDIs. FP/FORM was warmer, less forceful, had a longer plume duration and slower maximal velocity. These plume characteristics of FP/FORM may lead to improved lung deposition.. Mundipharma Research Limited, Cambridge, UK.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aerosol Propellants; Asthma; Bronchodilator Agents; Chemistry, Pharmaceutical; Drug Therapy, Combination; Fluticasone; Formoterol Fumarate; Hydrocarbons, Fluorinated; Metered Dose Inhalers; Nebulizers and Vaporizers; Salmeterol Xinafoate; Time Factors

Sublingual route, a noninjective way of allergen administration appears to be associated with a lower incidence of severe systemic reactions compared with the subcutaneous route. Local adverse reactions are reported which resolve spontaneously within a few days without need for discontinuation of treatment. Hereby, we report two pediatric cases, one with persistent asthma and the other one with persistent allergic rhinitis. Both were treated by house dust mite sublingual immunotherapy, one of whom developed severe wheezing (grade 2 systemic reaction based on World Allergy Organization subcutaneous systemic reaction grading system) and the other intractable vomiting (grade 3 local reaction based on World Allergy Organization sublingual immunotherapy local adverse events grading system) at the end of the build-up phase which repeated on re-administration of the same dose. Both of those two cases completed their 3-year immunotherapy successfully by patient-based adjustment of the highest tolerated dose of the maintenance.

Topics: Animals; Asthma; Child; Child, Preschool; Dermatophagoides farinae; Dermatophagoides pteronyssinus; Dose-Response Relationship, Immunologic; Fluticasone; Histamine Antagonists; Humans; Male; Maximum Tolerated Dose; Nausea; Respiratory Sounds; Rhinitis, Allergic; Sublingual Immunotherapy; Vomiting

The advent of highly active antiretroviral therapy for HIV infection dramatically changed the landscape of the disease. Ritonavir, a protease inhibitor (PI) frequently used in low doses to 'boost' the concentrations of other PIs, inhibits the cytochrome P450 3A4 isoenzyme, a common metabolic pathway to multiple drugs, so the potential for drug interactions is not negligible. A 39-year-old man with HIV-1 infection, treated with a ritonavir-boosted PI, was started on fluticasone/salmeterol inhaler and intranasal fluticasone, in 2009, in the setting of asthma and allergic rhinitis. In 2013, he presented with 1-year evolution of symptoms suggesting Cushing's syndrome, and was experiencing recurrent falls. A spine CT showed a vertical L3 fracture and thoracolumbar erosions; a bone density scan revealed severe osteoporosis. Hormonal assays were compatible with hypothalamic-pituitary-adrenal axis suppression, and iatrogenic Cushing's syndrome due to ritonavir-fluticasone interaction was considered. Fluticasone was suspended and oral corticosteroid replacement initiated, with a favourable outcome.

Topics: Accidental Falls; Adult; Anti-Allergic Agents; Asthma; Bronchodilator Agents; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Iatrogenic Disease; Male; Osteoporosis; Rhinitis, Allergic; Ritonavir

Topics: Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Fluticasone; Humans; Indans; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Quinolones; Salmeterol Xinafoate

Primary laryngeal aspergillosis is extremely rare, especially in an immunocompetent host. It is commonly found as a part of systemic infection in immunocompromised patients. A case of vocal cord aspergillosis with no systemic extension in an immunocompetent patient on long-term steroid metered dose inhaler (MDI) is presented here, because of its rarity. The present case is a 28-year-old asthmatic female who was on inhalational steroid for 8 years, presented with sudden onset of severe dysphonia for 5 days. Fiberoptic laryngoscopy demonstrated whitish plaque involving right vocal cord, clinically suggestive of fungal laryngitis. Microlaryngeal laser surgery was performed with stripping of the plaque. Histopathology demonstrated ulcerated hyperplastic squamous epithelium with masses of fungal hyphae, which was confirmed to be Aspergillus species on fungal culture. This rare but serious adverse effect of long-term steroid MDI use must be kept in mind while treating an asthmatic patient. We also present a brief review of literature of laryngeal aspergillosis.

Topics: Administration, Inhalation; Adult; Aspergillosis; Asthma; Female; Fluticasone; Humans; Laryngeal Diseases; Vocal Cords

Severe asthma and viral-induced asthma exacerbations represent a high unmet medical need as no therapy is currently available for these patients. HRV (human rhinovirus) is prominently associated with asthma exacerbations in humans. The aim of the present study was to establish a mouse model of severe asthma with additional rhinovirus infection to investigate the interplay between chronic allergic airway inflammation and acute respiratory viral infection. Balb/c mice were sensitized with HDM (house dust mite) extract (25 μg in 50 μl of saline) by i.n. (intranasal) delivery to the lung over 7 weeks. HRV1B (HRV serotype 1B) inoculation was performed i.n. on the last 3 days. Therapeutic treatment with FP (fluticasone propionate) was performed to assess steroid efficacy. Lung resistance was measured invasively to assess AHR (airway hyper-responsiveness). BAL (bronchoalveolar lavage) differential cell count, cytokines, lung histology and the proliferative and cytokine response of MLN (mediastinal lymph node) cells upon in vitro restimulation were analysed. Chronic HDM application induced a strong Th2-skewed eosinophilic airway inflammation and AHR, which was not exacerbated by superimposed HRV1B infection. Therapeutic steroid intervention in the chronic HDM model reduced BAL eosinophil cell counts, cytokine levels and AHR, while neutrophil numbers were unaffected. Steroid efficacy against inflammatory readouts was maintained during additional HRV1B infection. Animals with chronic allergic airway inflammation exhibited a diminished immune response towards superimposed HRV1B infection compared with HRV1B alone, as induction of the anti-viral and pro-inflammatory cytokines IFN (interferon)-α, IFN-γ and IL (interleukin)-12 were suppressed. Although superimposed HRV1B infection did not provoke asthma exacerbation in this severe model, a deficient anti-viral immune response to HRV1B was present under chronic allergic airway inflammatory conditions. Thus, this model is able to reflect some aspects of the complex interplay of respiratory virus infection in chronic allergic asthma.

Topics: Acute Disease; Allergens; Androstadienes; Animals; Asthma; Bronchoalveolar Lavage Fluid; Chronic Disease; Cytokines; Disease Models, Animal; Fluticasone; Glucocorticoids; Mice; Mice, Inbred BALB C; Picornaviridae Infections; Pyroglyphidae; Respiratory Tract Infections; Rhinovirus; Viral Load

We sought to understand if pediatrician characteristics and asthma assessment and treatment varied in association with the proportion of African-American and Latino children in the pediatrician's practice.. We conducted a cross-sectional survey of 500 American Academy of Pediatrics members between November 2005 and May 2006. Standardized vignettes were used to test how different indicators of a patient's asthma status affect pediatrician asthma assessments and recommendations. Linear and logistic regression models were used to examine the association of pediatrician assessments and treatment recommendations for these vignettes, respectively, with the proportion of reported African-American and Latino children seen in their practice.. There were 270 respondents (response rate = 54%). Based on pediatrician-reported percentage of minority patients, there were no differences in board certification status, recognition of poorly controlled asthma nor in the likelihood of appropriately increasing long-term controller medications to treat poorly controlled asthma (p > 0.05 for all analyses).. Caring primarily for minority children by AAP pediatricians appears unrelated to training qualifications or in their reported knowledge of how to appropriately assess and treat asthma. Therefore, studies of asthma care disparities should focus on understanding the knowledge-base of non-AAP pediatric providers who care for minority populations and exploring other potential contributory provider-level factors (e.g. communication skills).

Topics: Androstadienes; Asthma; Black or African American; Bronchodilator Agents; Certification; Data Collection; Female; Fluticasone; Healthcare Disparities; Hispanic or Latino; Humans; Male; Minority Groups; Pediatrics; Physicians; Racial Groups; Specialization

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Asthma; Clinical Trials as Topic; Fluticasone; Humans; Phthalazines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Glands; Adrenocorticotropic Hormone; Androstadienes; Anti-Asthmatic Agents; Asthma; Biomarkers; Bronchodilator Agents; Cushing Syndrome; Drug Administration Schedule; Female; Fluticasone; Humans; Hydrocortisone; Middle Aged

Obstructive sleep apnea is prevalent among people with asthma, but underlying mechanisms remain unknown. Inhaled corticosteroids may contribute. We tested the effects of orally inhaled fluticasone propionate (FP) on upper airway (UAW) during sleep and wakefulness.. 16-week single-arm study.. 18 (14 females, mean [ ± SD] age 26 ± 6 years) corticosteroid-naïve subjects with mild asthma (FEV1 89 ± 8% predicted).. High dose (1,760 mcg/day) inhaled FP.. (1) UAW collapsibility (passive critical closing pressure [Pcrit]); (2) tongue strength (maximum isometric pressure-Pmax, in KPa) and endurance-time (in seconds) able to maintain 50% Pmax across 3 trials (Ttot)-at anterior and posterior locations; (3) fat fraction and volume around UAW, measured by magnetic resonance imaging in three subjects.. Pcrit overall improved (became more negative) (mean ± SE) (-8.2 ± 1.1 vs. -12.2 ± 2.2 cm H2O, p = 0.04); the response was dependent upon baseline characteristics, with older, male gender, and worse asthma control predicting Pcrit deterioration (less negative). Overall, Pmax increased (anterior p = 0.02; posterior p = 0.002), but Ttot generally subsided (anterior p = 0.0007; posterior p = 0.06), unrelated to Pcrit response. In subjects studied with MRI, fat fraction and volume increased by 20.6% and 15.4%, respectively, without Pcrit changes, while asthma control appeared improved.. In this study of young, predominantly female, otherwise healthy subjects with well-controlled asthma and stiff upper airways, 16-week high dose FP treatment elicited Pcrit changes which may be dependent upon baseline characteristics, and determined by synchronous and reciprocally counteracting local and lower airway effects. The long-term implications of these changes on sleep disordered breathing severity remain to be determined.

Topics: Administration, Inhalation; Adult; Age Factors; Airway Obstruction; Androstadienes; Asthma; Bronchodilator Agents; Female; Fluticasone; Humans; Male; Pilot Projects; Polysomnography; Sex Factors; Sleep; Sleep Apnea, Obstructive; Wakefulness

Recent asthma guidelines endorse the safety of long-acting β2-agonists (LABAs) and of mild and moderate doses of inhaled corticosteroids (ICSs) when required to control asthma during pregnancy, yet do not state a preferred medication within each class.. To estimate the relative perinatal safety with the use of salmeterol and formoterol (LABAs) and that of fluticasone and budesonide (ICSs) during pregnancy.. A subcohort of pregnancies from asthmatic women was selected from health care administrative databases of Quebec, Canada. Low birth weight (LBW) was defined as weight less than 2,500 g, preterm birth (PB) as delivery before 37 weeks of gestation, and small for gestational age (SGA) as a birth weight below the 10th percentile. The effect of treatment with salmeterol vs formoterol and fluticasone vs budesonide on the outcomes was determined with generalized estimating equation models.. The LABA and ICS subcohorts were composed of 547 (385 salmeterol and 162 formoterol users) and 3,798 (3,190 fluticasone and 608 budesonide users) pregnancies, respectively. No statistically significant differences were observed for LBW (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.44-1.88), PB (OR, 1.11; 95% CI, 0.56-2.23), and SGA (OR, 1.16; 95% CI, 0.67-2.02) newborns between women exposed to salmeterol vs formoterol or between women exposed to fluticasone vs budesonide (LBW: OR, 1.08; 95% CI, 0.76-1.52; PB: OR, 1.07; 95% CI, 0.78-1.49; and SGA, OR: 1.10; 95% CI, 0.85-1.44).. This study does not provide evidence of greater perinatal safety for one LABA or one ICS over the other.

Topics: Adolescent; Adrenergic beta-2 Receptor Agonists; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Canada; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Infant, Low Birth Weight; Pregnancy; Pregnancy Complications; Premature Birth; Salmeterol Xinafoate; Treatment Outcome; Young Adult

Feline demodicosis due to Demodex cati is a rare skin disease often associated with concurrent disease and generalized immunosuppression. Local immunosuppression due to the application of topical immunomodulatory drugs, such as glucocorticoids and tacrolimus, or by tumour cells has been suggested as a potential trigger for development of localized demodicosis in humans and animals.. The goal was to describe two cats with asthma that developed localized demodicosis on the muzzle as a result of chronic therapy with a glucocorticoid administered via dispensing inhaler mask.. In both cats, the muzzle area exposed to the fluticasone-dispensing chamber exhibited patchy alopecia, mild erythema, crusting and scaling. Deep skin scraping revealed D. cati. Discontinuation or reduction of fluticasone and administration of milbemycin resulted in resolution of clinical signs within 2 months in both cats. A negative skin scrape was obtained after 7 months of milbemycin in one of the cats.. Demodicosis should be considered as a possible differential diagnosis in cats with primary alopecia or other skin lesions on the face exposed to inhalant glucocorticoids. Minimization of contact between the inhalant glucocorticoid and the skin can be achieved by wiping residual powder from the face and by keeping the mask tightly pressed to the skin to avoid contact with the surrounding area.

Topics: Aerosols; Androstadienes; Animals; Anthelmintics; Anti-Inflammatory Agents; Asthma; Cat Diseases; Cats; Fluticasone; Macrolides; Male; Mite Infestations; Mites; Nebulizers and Vaporizers; Respiratory Therapy

A new combination inhaler containing fluticasone, a potent inhaled corticosteroid (ICS), and formoterol, a long-acting β-agonist (LABA) with rapid onset and sustained bronchodilator effect, has been approved for treatment of persistent asthma in patients ≥12 years of age requiring combination ICS-LABA therapy. The fluticasone/formoterol combination, delivered via pressurized metered-dose inhaler and available in three dose strengths, has demonstrated a good safety and tolerability profile in trials of up to 1 year. The efficacy of fluticasone/formoterol is greater than that of fluticasone or formoterol alone and noninferior to that of fluticasone/salmeterol and budesonide/formoterol in tightly controlled 8-12-week clinical trials. Advantages of the fluticasone/formoterol combination aerosol include rapid onset of bronchodilation, an attribute preferred by patients, and emission of a high fine-particle fraction that is consistent at different flow rates, which may aid consistency of delivery (given patient variability in inhalation maneuvers) and provide real-life benefits.

Topics: Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Aerosols; Androstadienes; Asthma; Bronchodilator Agents; Clinical Trials, Phase III as Topic; Drug Combinations; Ethanolamines; Fluticasone; Forced Expiratory Volume; Formoterol Fumarate; Humans; Particle Size; Randomized Controlled Trials as Topic; Treatment Outcome

T lymphocytes are involved in the pathogenesis of nonallergic asthma. The objective of this study was to characterize the subset distribution and pattern of chemokine receptor expression in circulating T lymphocyte subsets from nonallergic asthma patients.. Forty stable nonallergic asthma patients and 16 sex- and age-matched healthy donors were studied. Twelve patients did not receive inhaled steroids (untreated patients), 16 received 50-500 μg b.i.d. of inhaled fluticasone propionate (FP) (standard-dose patients), and 12 received over 500 μg b.i.d. of inhaled FP (high-dose patients) for at least 12 months prior to the beginning of this study and were clinically well controlled. Flow cytometry was performed using a panel of monoclonal antibodies (4 colors).. Nonallergic asthma patients treated with high doses of inhaled FP showed a significant reduction in the percentages of CD3+ T lymphocytes compared to healthy controls. Untreated patients showed a significant increase in CCR6 expression in CD8+CD25+ and CD8+CD25+bright T cells compared to healthy controls. The results were similar for CXCR3 and CCR5 expression. In patients treated with standard doses of FP, CCR5 expression was significantly increased in CD3+ T lymphocytes relative to healthy controls.. The different groups of clinically stable nonallergic asthmatic patients showed distinct patterns of alterations in subset distribution as well as CCR6, CXCR3, and CCR5 expression on circulating T lymphocytes. .

Topics: Androstadienes; Asthma; CD3 Complex; CD8 Antigens; Cross-Sectional Studies; Female; Fluticasone; Humans; Interleukin-2 Receptor alpha Subunit; Leukocyte Common Antigens; Lymphocyte Count; Male; Middle Aged; Receptors, CCR5; Receptors, CCR6; Receptors, CXCR3; Skin Tests; T-Lymphocytes

Overexpression of the (+)insert smooth muscle myosin heavy chain (SMMHC) isoform could contribute to airway bronchospasm by increasing the velocity of contraction. Whether the (+)insert isoform is present in the small airways and its expression is reversible in asthma are unknown.. To determine the anatomical location and the expression kinetics of the (+)insert SMMHC isoform in airways of horses with heaves and to evaluate its modulation in response to disease status.. We evaluated the (+)insert SMMHC isoform in the airways of horses with heaves during disease exacerbation and remission, and in controls. The expression kinetics of the SMMHC (+)insert was then assessed at multiple time points in two studies: first, in horses with heaves treated for a 1-year period with antigen avoidance alone, inhaled corticosteroids alone or both; second, in horses with heaves before and after a 30-day natural antigen exposure. Gene expression analysis was assessed by quantitative PCR and protein expression was confirmed by targeted mass spectrometry.. The (+)insert SMMHC isoform was significantly increased in central and peripheral airways, but not in the trachea of heaves-affected horses in clinical exacerbation when compared horses with heaves in remission and controls. Both corticosteroid administration and antigen avoidance led to a significant reduction of the (+)insert expression in the airways. The (+)insert SMMHC isoform was not significantly increased in airways after 1 month of antigenic re-exposure.. The (+)insert SMMHC expression is increased throughout the bronchial tree in horses with heaves and reversible by corticosteroids administration and antigen avoidance.

Topics: Administration, Inhalation; Androstadienes; Animals; Antigens; Asthma; Bronchi; Bronchoalveolar Lavage Fluid; Female; Fluticasone; Gene Expression Regulation; Glucocorticoids; Horse Diseases; Horses; Male; Muscle, Smooth; Myosin Heavy Chains; Protein Isoforms; Remission Induction; Smooth Muscle Myosins; Trachea

Allergic rhinitis is a very common disease that causes high economic costs. Furthermore inadequate treatment can lead to bronchial asthma. Against this background, drugs for the treatment of allergic rhinitis should be evaluated from a comprehensive medical-economic perspective. The new combination of an antihistamine and a corticosteroid, introduced in the market in 2013, emerges as useful pharmaceutical alternative, both with regard to the medical outcome parameters as well as cost-effectiveness.

Topics: Absenteeism; Administration, Intranasal; Adolescent; Adult; Androstadienes; Asthma; Child; Child, Preschool; Cost-Benefit Analysis; Drug Combinations; Female; Fluticasone; Germany; Humans; Male; National Health Programs; Phthalazines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Socioeconomic Factors

Chronic rhinosinusitis and asthma are expressions of airway inflammatory diseases that frequently coexist, especially in the case of adult-onset asthma. Both conditions have similar pathological features, while one affects the upper airways and the other the lower airways. Whether the treatment of bronchial inflammation affects the severity of sinus disease remains an unanswered question. We report a case of refractory chronic rhinosinusitis with co-morbid adult-onset asthma that effectively improved upon treatment with a daily dose of 200 μg (100 μg b.i.d.) of inhaled fluticasone propionate (FP).

Topics: Administration, Inhalation; Androstadienes; Asthma; Bronchodilator Agents; Chronic Disease; Female; Fluticasone; Humans; Middle Aged; Rhinitis; Sinusitis; Treatment Outcome

Omalizumab has been shown to reduce exacerbation rates in moderate to severe allergic asthma. Our aim was to evaluate omalizumab efficacy and safety in a real-life setting in severe asthmatic children. 104 children (aged 6-18 years), followed up in paediatric pulmonary tertiary care centres, were included at the beginning of omalizumab treatment. Asthma control levels, exacerbations, inhaled corticosteroid dose, lung function and adverse events were evaluated over 1 year. Children were characterised by allergic sensitisation to three or more allergens (66%), high IgE levels (mean 1125 kU · L(-1)), high rate of exacerbations (4.4 per year) and healthcare use during the previous year, and high inhaled corticosteroid dose (mean 703 μg equivalent fluticasone per day). Asthma control levels defined as good, partial or poor, improved from 0%, 18% and 82% at entry to 53%, 30% and 17% at week 20, and to 67%, 25% and 8% at week 52, respectively (p<0.0001). Exacerbation and hospitalisation rates dropped by 72% and 88.5%, respectively. At 12 months, forced expiratory volume in 1 s improved by 4.9% (p=0.023), and inhaled corticosteroid dose decreased by 30% (p<0.001). Six patients stopped omalizumab for related significant adverse events. Omalizumab improved asthma control in children with severe allergic asthma and was generally well tolerated. The observed benefit was greater than that reported in clinical trials.

Topics: Administration, Oral; Adolescent; Adrenal Cortex Hormones; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Asthma; Child; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Humans; Hypersensitivity; Immunoglobulin E; Male; Omalizumab; Respiratory Function Tests; Treatment Outcome

In vitro measures of aerosol particles size, such as the fine particle mass, play a pivotal role for approval of inhaled anti-asthmatic drugs. However, the validity as a measure of dose to the lungs in children lacks evidence. In this study we investigated for the first time the association between an in vivo estimate of lung dose of inhaled drug in children and the corresponding particle size segments assessed ex vivo. Lung dose of fluticasone propionate after inhalation from a dry powder inhaler (Diskus®) was studied in 23 children aged 4-7 and 12-15 years with mild asthma. Six-hour pharmacokinetics was assessed after single inhalation. The corresponding emitted mass of drug in segments of aerosol particle size was assessed ex vivo by replicating the inhalation flows recorded by transducers built into the Diskus® inhaler and re-playing them in a breathing simulator. There was no correlation between any inhaled particle size segment and lung dose assessed by pharmacokinetics and adjusted for age and body size. Measures of particles size segments were not related to lung dose in children. Until further evidence is provided it may be warranted to emphasize pharmacokinetic or pharmacodynamic assessments of drug delivery to the lung.

Topics: Administration, Inhalation; Adolescent; Aerosols; Androstadienes; Anti-Asthmatic Agents; Area Under Curve; Asthma; Child; Child, Preschool; Female; Fluticasone; Humans; Lung; Male; Nebulizers and Vaporizers; Particle Size

Characteristics of inhaled corticosteroids (ICSs) differ, but data comparing the real-life effectiveness of various ICSs for asthma are lacking.. We sought to compare real-life asthma outcomes and costs of extrafine hydrofluoroalkane (HFA)-beclomethasone and fluticasone administered through a pressurized metered-dose inhaler.. This retrospective matched cohort study examined database markers of asthma control from a large US longitudinal health care claims database over 1 baseline and 1 outcome year for 10,312 patients with asthma aged 12 to 80 years receiving their first ICS as HFA-beclomethasone or fluticasone and matched on baseline demographic characteristics and asthma severity.. Patients started on HFA-beclomethasone had significantly higher odds (adjusted odds ratio, 1.19; 95% CI; 1.08-1.31) of achieving overall control (risk and impairment), which was defined as no hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory tract infection and less than 2 puffs per day of short-acting β-agonist; they also experienced a lower rate of respiratory-related hospitalizations or referrals (adjusted rate ratio, 0.82; 95% CI, 0.73-0.93) than patients started on fluticasone. Other database outcome measures were similar in the 2 cohorts. Prescribed HFA-beclomethasone doses were lower (P < .001) than fluticasone doses (median, 320 μg/d [interquartile range, 160-320 μg/d] vs 440 μg/d [interquartile range, 176-440 μg/d]). Adjusted respiratory-related health care costs were significantly lower for HFA-beclomethasone than fluticasone (mean, $1869 [95% CI, $1727-$2032] vs $2259 [95% CI, $2111-$2404]), representing a mean annual savings of $390 (95% CI, $165-$620) per patient prescribed HFA-beclomethasone rather than fluticasone.. Asthma treatment outcomes were similar or better with HFA-beclomethasone prescribed at significantly lower doses and with lower costs than fluticasone.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Cohort Studies; Female; Fluticasone; Health Care Costs; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Middle Aged; Retrospective Studies

In Argentina, more than 3 million people suffer from asthma, with numbers rising. When asthma patients acquire viral infections which, in turn, trigger the asthmatic response, they may develop subsequent bacterial infections, mainly by Streptococcus (S.) pneumoniae. This encapsulated Gram(+) bacterium has been considered historically a T cell-independent antigen. Nevertheless, several papers describe the role of T cells in the immune response to S. pneumoniae. We evaluated the response to S. pneumoniae and compared it to the response to Mycobacterium (M.) tuberculosis, a different type of bacterium that requires a T helper type 1 (Th1) response, in cells from atopic asthmatic children, to compare parameters for the same individual under exacerbation and in a stable situation whenever possible. We studied asthma patients and a control group of age-matched children, evaluating cell populations, activation markers and cytokine production by flow cytometry, and cytokine concentration in serum and cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). No differences were observed in γδ T cells for the same patient in either situation, and a tendency to lower percentages of CD4(+) CD25(hi) T cells was observed under stability. A significantly lower production of tumour necrosis factor (TNF)-α and a significantly higher production of interleukin (IL)-5 was observed in asthma patients compared to healthy individuals, but no differences could be observed for IL-4, IL-13 or IL-10. A greater early activation response against M. tuberculosis, compared to S. pneumoniae, was observed in the asthmatic patients' cells. This may contribute to explaining why these patients frequently acquire infections caused by the latter bacterium and not the former.

Topics: Adolescent; Androstadienes; Anti-Asthmatic Agents; Antigens, Bacterial; Asthma; BCG Vaccine; Cells, Cultured; Child; Cytokines; Female; Fluticasone; Humans; Immunophenotyping; Interferon-gamma; Leukocytes, Mononuclear; Lymphocyte Activation; Male; Mycobacterium tuberculosis; Streptococcus pneumoniae; T-Lymphocyte Subsets; Th2 Cells; Young Adult

Viral infection can exacerbate asthma by inducing the accumulation of inflammatory cells in the airway. We have previously reported that double-stranded RNA (dsRNA), a viral product and ligand of the Toll-like receptor-3 (TLR3), activates the transcription factors NF-κB and IRF-3 and upregulates the expression of inflammatory chemokines in airway epithelial cells. Here, we examined the effects of the glucocorticoid fluticasone propionate (FP) on the expression of the inflammatory chemokines CCL5, CXCL8 and CXCL10.. The airway epithelial cell line BEAS-2B was used for this study. Expression of CCL5, CXCL8 and CXCL10 mRNA and protein was quantified by real-time PCR and ELISA assay, respectively. To examine the association of FP with the physiology of chemokine production, we included several methods. Nuclear translocation of transcription factors was determined by performing Western blot analysis. Histone deacetylase (HDAC) activity in nuclear extracts was measured using a colorimetric assay. Stability of the chemokine mRNAs was examined in cells incubated with actinomycin D. The activities of the CCL5 promoter and the transcription factors NF-κB and IRF-3 were assessed using luciferase reporter assays.. Treatment of BEAS-2B cells with FP significantly and dose-dependently (10(-9) to 10(-6)M) inhibited dsRNA-induced expression of CCL5, CXCL8 and CXCL10 protein and mRNA, but did not affect mRNA stability. FP also significantly inhibited dsRNA-stimulated CCL5 promoter activity. However, FP had no effect on the activity of HDAC or the nuclear translocation of NF-κB and IRF-3.. FP inhibits the dsRNA-stimulated expression of inflammatory chemokines in airway epithelial cells. FP may act by inhibiting chemokine transcription through an as yet unidentified mechanism.

Topics: Androstadienes; Anti-Allergic Agents; Asthma; Cell Line; Cell Nucleus; Chemokine CCL5; Chemokines; Fluticasone; Gene Expression Regulation; Histone Acetyltransferases; Humans; Inflammation Mediators; Poly I-C; Promoter Regions, Genetic; Protein Transport; RNA Stability; RNA, Messenger; Transcription Factors; Transcriptional Activation

In practice it is logical that inhalers are prescribed only after patients have received training and demonstrated their ability to use the device. However, many patients are unable to use their pressurised metered-dose inhaler devices (pMDIs) correctly. We assessed the relationship between asthma control and patients' ability to use their prescribed pMDIs.. Evaluation of 3,981 (46% male) primary care asthma patient reviews, which included inhaler technique and asthma control, by specialist nurses in primary care in 2009. The paper focuses on people currently prescribed pMDI devices.. Accurate data on reliever and preventer inhaler prescriptions were available for 3,686 and 2,887 patients, respectively. In patients prescribed reliever inhalers, 2,375 (64%) and 525 (14%) were on pMDI alone or pMDI plus spacer, respectively. For those prescribed preventers, 1,976 (68%) and 171 (6%) were using a pMDI without and with a spacer, respectively. Asthma was controlled in 50% of patients reviewed. The majority of patients (60% of 3,686) were using reliever pMDIs, 13% with spacers. Incorrect pMDI use was associated with poor asthma control (p<0.0001) and more short burst systemic steroid prescriptions in the last year (p=0.038). Of patients using beclometasone (the most frequently prescribed preventer drug in our sample), significantly more of those using a breath-actuated pMDI device (p<0.0001) and a spacer (p<0.0001) were controlled compared with those on pMDIs alone.. Patients who are able to use pMDIs correctly have better asthma control as defined by the GINA strategy document. Beclometasone via a spacer or breath-actuated device resulted in better asthma control than via a pMDI alone. Patients prescribed pMDIs should be carefully instructed in technique and have their ability to use these devices tested; those unable to use the device should be prescribed a spacer or an alternative device such as one that is breath-actuated.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Albuterol; Androstadienes; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Drug Combinations; Ethanolamines; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Formoterol Fumarate; Glucocorticoids; Humans; Inhalation Spacers; Male; Metered Dose Inhalers; Middle Aged; Mometasone Furoate; Patient Education as Topic; Pregnadienediols; Retrospective Studies; Self Administration; Treatment Outcome; Young Adult

It has been suggested that smoking asthmatics benefit less from corticosteroid treatment than never-smoking asthmatics. We investigated differences in blood and sputum inflammatory profiles between ex-, current-, and never-smokers and assessed their ICS treatment response after 2-week and 1-year treatment.. We analyzed FEV1, PC20 methacholine and PC20 AMP, (differential) cell counts in sputum and blood in ex-, current- and never-smokers at baseline (n=114), after 2-week treatment with fluticasone 500 or 2000 μg/day (n=76) and after 1-year treatment with fluticasone 500 μg/day or a variable dose of fluticasone based on a self-management plan (n=64).. A total of 114 patients were included (29 ex-, 30 current- and 55 never-smokers. At baseline, ex- and current-smokers had less eosinophils in sputum and blood than never-smokers. Blood neutrophil counts were higher in current- than in never-smokers. A higher number of cigarettes smoked daily was associated with lower blood and sputum eosinophils. After 2-week ICS treatment, FEV1 %predicted improved less in current-smokers than never-smokers (2.4% versus 8.1%, p=0.010) and ex-smokers tended to improve less than never-smokers (4.1%, p=0.067). In contrast, no differences in ICS treatment response in lung function or inflammatory cells were found between the three groups after 1 year.. Ex- and current-smokers have less eosinophils and more neutrophils in their sputum and blood than never-smokers. Although ex- and current-smokers have a reduced short-term corticosteroid treatment response, we did not find a difference in their long-term treatment response.

Topics: Adult; Androstadienes; Anti-Inflammatory Agents; Asthma; Biomarkers; Bronchial Provocation Tests; Eosinophils; Female; Fluticasone; Forced Expiratory Volume; Humans; Inflammation; Leukocyte Count; Male; Neutrophils; Smoking; Smoking Cessation; Sputum

The economic burden of asthma on the UK National Health Service (NHS) is the largest among allergic diseases. Current asthma guidelines recommend adding a long acting β2-agonist (LABA) to a low-dose inhaled corticosteroid (ICS) in patients who are on ICS monotherapy and have uncontrolled asthma. The fixed-dose combination of fluticasone propionate and salmeterol xinafoate (FP/SAL), available in a pressurized metered-dose inhaler (pMDI) device, is the most commonly prescribed ICS/LABA combination. An additional fixed-dose combination of fluticasone propionate and formoterol fumarate (FP/FORM) in pMDI is now available. In a 12-week non-inferiority study, FP/FORM demonstrated comparable efficacy to FP/SAL. The present analysis estimates the annual budget impact for the UK NHS using FP/FORM as an alternative to FP/SAL.. Current pMDI prescribing data were from a real-world UK patient database (Cegedim Strategic Data). Annual costs to the NHS for drug acquisition, administration, and monitoring were estimated for FP/FORM and FP/SAL and used to assess the potential budget impact for the NHS for the use of FP/FORM instead of FP/SAL. Varying rates of uptake, adherence, adverse event-related costs, and resource use associated with switching treatment were assessed in scenario analyses.. Assuming similar levels of ICS use with both regimens, annual drug acquisition costs per person were lower with FP/FORM (£412) than with FP/SAL (£509). The difference in acquisition costs and otherwise comparable input costs between the treatments, results in potential annual savings of £15,110,279 to the NHS, assuming uptake of FP/FORM over FP/SAL in 50% of existing patients. The introduction of FP/FORM results in cost savings for the NHS in all of the assessed scenario analyses.. The comparable efficacy and lower acquisition costs of FP/FORM compared with FP/SAL make it a cost-saving option for the UK NHS for the treatment of asthma patients requiring combination maintenance therapy using a pMDI.

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Cost-Benefit Analysis; Drug Combinations; Drug Costs; Drug Substitution; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Metered Dose Inhalers; State Medicine; United Kingdom

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Combinations; Drug Interactions; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Young Adult

The interpatient variability in response to asthma controllers is significant and associates with pharmacogenomic variability. The goal of the present study was to identify novel variants that associate with response to common asthma controllers: fluticasone, combination of fluticasone + salmeterol and montelukast with single nucleotide polymorphisms (SNPs) in β2-adrenergic receptor, corticosteroid and leukotriene pathway candidate genes. Participants in a large clinical trial of step-down strategies volunteered for this pharmacogenetic study. A total of 169 SNPs in 26 candidate genes were genotyped in 189 Caucasian participants with asthma who took either fluticasone (100 μg bid), fluticasone propionate (100 μg) + salmeterol (50 μg) (FP/Salm) or montelukast (5 or 10 mg) each night for 16 weeks. Primary outcomes were the slopes of plots of Asthma Control Questionnaire (ACQ) scores versus time following randomization; and the percent change in percent predicted FEV1 (ΔFEV1%pred) from enrollment to the end of the study. Associations between SNPs and outcomes were analyzed using general linear models. False discovery rate and Bonferroni corrections were used to correct for multiple comparisons. In all, 16 SNPs in seven genes were significantly associated with outcomes. For FP/Salm, three SNPs in CHRM2 associated with ACQ slope (P=2.8 × 10⁻⁵), and rs1461496 in HSPA8 associated with ΔFEV1%pred. For fluticasone, five SNPs in CRHR1 (P=1.9 × 10⁻⁴), and three SNPs in COL2A1 associated with ACQ slope and ΔFEV1%pred, respectively. For montelukast, four SNPs in CHRM2 associated with ΔFEV1%pred and predicted an opposite effect compared with fluticasone (P=9 × 10⁻³). The present study indentified several novel SNPs that associate with response to common asthma controllers, and support further pharmacogenomic study and the use of genetic variants to personalize asthma treatment.

Topics: Acetates; Administration, Inhalation; Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Clinical Trials as Topic; Cyclopropanes; Drug Combinations; Female; Fluticasone; Forced Expiratory Volume; Genetic Association Studies; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Precision Medicine; Quinolines; Receptors, Adrenergic, beta-2; Salmeterol Xinafoate; Sulfides

Chronic respiratory disease and inhaled corticosteroid (ICS) therapy for chronic obstructive pulmonary disease (COPD) increase the risk of pneumonia. Few data are available on the association of these risk factors with non-tuberculous mycobacterial (NTM) pulmonary disease.. This study examined chronic respiratory diseases and ICS use as risk factors in a population-based case-control study encompassing all adults in Denmark with microbiologically confirmed NTM pulmonary disease between 1997 and 2008. The study included 10 matched population controls per case. Conditional logistic regression was used to compute adjusted ORs for NTM pulmonary disease with regard to chronic respiratory disease history.. Overall, chronic respiratory disease was associated with a 16.5-fold (95% CI 12.2 to 22.2) increased risk of NTM pulmonary disease. The adjusted OR for NTM disease was 15.7 (95% CI 11.4 to 21.5) for COPD, 7.8 (95% CI 5.2 to 11.6) for asthma, 9.8 (95% CI 2.03 to 52.8) for pneumoconiosis, 187.5 (95% CI 24.8 to 1417.4) for bronchiectasis, and 178.3 (95% CI 55.4 to 574.3) for tuberculosis history. ORs were 29.1 (95% CI 13.3 to 63.8) for patients with COPD on current ICS therapy and 7.6 (95% CI 3.4 to 16.8) for patients with COPD who had never received ICS therapy. Among patients with COPD, ORs increased according to ICS dose, from 28.1 for low-dose intake to 47.5 for high-dose intake (more than 800 μg/day). The OR was higher for fluticasone than for budesonide.. Chronic respiratory disease, particularly COPD treated with ICS therapy, is a strong risk factor for NTM pulmonary disease.

Topics: Administration, Inhalation; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Bronchiectasis; Budesonide; Case-Control Studies; Chronic Disease; Confidence Intervals; Denmark; Female; Fluticasone; Humans; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Odds Ratio; Pneumoconiosis; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Risk Factors; Tuberculosis, Pulmonary

To determine the relationship between allelic variations in genes involved in fluticasone propionate (FP) metabolism and asthma control among children with asthma managed with inhaled FP.. The relationship between variability in asthma control scores and genetic variation in drug metabolism was assessed by genotyping 9 single nucleotide polymorphisms in the CYP3A4, CYP3A5, and CYP3A7 genes. Genotype information was compared with asthma control scores (0=well controlled to 15=poorly controlled), determined using a questionnaire modified from the National Heart Lung and Blood Institute's Expert Panel 3 guidelines.. Our study cohort comprised 734 children with asthma (mean age, 8.8±4.3 years) and was predominantly male (61%) and non-Hispanic white (53%). More than one-half of the children (56%; n=413) were receiving an inhaled glucocorticoid daily, with FP the most frequently prescribed agent (65%). Among the children receiving daily FP, single nucleotide polymorphisms in CYP3A5 and CYP3A7 were not associated with asthma control scores. In contrast, asthma control scores were significantly improved in the 20 children (7%) with the CYP3A4*22 allele (median, 3; range, 0-6) compared with the 201 children without the CYP3A4*22 allele (median, 4; range, 0-15; P=.02). The presence of CYP3A4*22 was associated with improved asthma control scores by 2.1 points (95% CI, 0.5-3.8).. The presence of CYP3A4*22, which is associated with decreased hepatic CYP3A4 expression and activity, was accompanied by improved asthma control in the FP-treated children. Decreased CYP3A4 activity may improve asthma control with inhaled FP.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Asthma; Bronchodilator Agents; Child; Child, Preschool; Cytochrome P-450 CYP3A; Female; Fluticasone; Humans; Male; Pharmacogenetics; Polymorphism, Genetic; Prospective Studies; Surveys and Questionnaires

The choice among the different treatments available can have a great impact on the costs of asthma,. The objective of this study was to estimate the incremental cost-utility ratio of three inhaled corticosteroids (ICs): budesonide (BUD), fluticasone propionate (FP), and ciclesonide, compared to beclomethasone dipropionate (BDP) (the only IC included in the Compulsory Health Insurance Plan of Colombia),. A Markov-type model was developed to estimate costs and health outcomes of a simulated cohort of patients less than 18 years of age with persistent asthma treated over a 12-month period. Effectiveness parameters were obtained from a systematic review of the literature. Cost data were obtained from a hospital´s bills and from the national manual of drug prices. The study assumed the perspective of the national healthcare in Colombia. The main outcome was the variable "quality-adjusted life years" (QALY), RESULTS: While treatment with BDP was associated with the lowest cost (£106.16 average cost per patient during 12 months), treatment with FP resulted in the greatest gain in QUALYs (0.9325 QALYs). FP was associated with a greater gain in QALYs compared to BUD and ciclesonide (0.9325 vs. 0.8999 and 0.9051 QALYs, respectively) at lower costs (£231.19 vs. £309.27 and £270.15, respectively), thus leading to dominance. The incremental cost-utility ratio of FP compared to BDP was £19,835.28 per QALY, CONCLUSIONS: BDP is the most cost-effective therapy for treating pediatric patients with persistent asthma when willingness to pay (WTP) is less than £21,129.22/QALY, otherwise, FP is the most cost-effective therapy.

Topics: Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Cohort Studies; Colombia; Computer Simulation; Cost-Benefit Analysis; Drug Costs; Female; Fluticasone; Humans; Male; Markov Chains; Models, Economic; Pregnenediones; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic

An Afro-Caribbean girl showed localized hair depigmentation during treatment with inhaled fluticasone propionate. Although skin depigmentation is common after topical use of corticosteroids, hair depigmentation has never been reported with inhaled corticosteroids. The mechanisms underlying corticosteroid-induced skin depigmentation are not completely understood, but accepted hypotheses suggest a direct cytotoxic effect, changes in ground substance, vasoconstriction, mechanical effects of edema, or a dysregulation of melanogenesis.

Topics: Androstadienes; Animals; Anti-Allergic Agents; Asthma; Child, Preschool; Conjunctivitis; Edema; Female; Fluticasone; Hair Color; Hair Diseases; Humans; Pyroglyphidae; Respiratory Hypersensitivity; Rhinitis, Allergic, Perennial; Vasoconstriction

Glucocorticoid inhalation is the preferred asthma treatment during pregnancy. Previous studies on its safety focused on obstetric outcomes and offspring malformations.. To determine whether glucocorticoid inhalation during pregnancy is a risk factor for offspring pediatric diseases.. We studied offspring (live singletons) of pregnant women suffering from asthma during pregnancy (prevalence = 6.3%; n = 4,083 mother-child pairs) from the Danish National Birth Cohort (births, 1996-2002; prospective data). We estimated the associations between use of inhaled glucocorticoids for asthma treatment during pregnancy (n = 1231; 79.9% budesonide, 17.6% fluticasone, 5.4% beclomethasone, and 0.9% other or unspecified glucocorticoids) and offspring diseases (International Classification of Diseases-10th Revision, diagnoses) during childhood. We conducted Cox or logistic regression analyses for each International Classification of Diseases-10th Revision category, controlling for use of non-glucocorticoid-containing inhalants, and confirmed results by addressing confounding by treatment indication using propensity score.. Offspring median age at end of follow-up was 6.1 (range, 3.6-8.9) years. Glucocorticoid inhalation was not associated with offspring disease risk in most categories, except for offspring endocrine, metabolic, and nutritional disorders (hazard ratio, 1.84; 95% confidence interval, 1.13-2.99). When repeating analyses with the major subgroup that used budesonide only, association estimates were of similar magnitude.. Regarding most disease categories, data are reassuring, supporting the use of inhaled glucocorticoids during pregnancy. In line with animal data, glucocorticoid inhalation during pregnancy may be a risk factor for offspring endocrine and metabolic disturbances, which should be considered further.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Child, Preschool; Denmark; Endocrine System Diseases; Female; Fluticasone; Glucocorticoids; Humans; Logistic Models; Male; Metabolic Diseases; Morbidity; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Proportional Hazards Models; Risk Factors

Approximately 4% to 12% of pregnant women have asthma; few studies have examined the effects of maternal asthma medication use on birth defects. We examined whether maternal asthma medication use during early pregnancy increased the risk of selected birth defects.. National Birth Defects Prevention Study data for 2853 infants with 1 or more selected birth defects (diaphragmatic hernia, esophageal atresia, small intestinal atresia, anorectal atresia, neural tube defects, omphalocele, or limb deficiencies) and 6726 unaffected control infants delivered from October 1997 through December 2005 were analyzed. Mothers of cases and controls provided telephone interviews of medication use and additional potential risk factors. Exposure was defined as maternal periconceptional (1 month prior through the third month of pregnancy) asthma medication use (bronchodilator or anti-inflammatory). Associations between maternal periconceptional asthma medication use and individual major birth defects were estimated by using adjusted odds ratios (aOR) and 95% confidence intervals (95%CI).. No statistically significant associations were observed for maternal periconceptional asthma medication use and most defects studied; however, positive associations were observed between maternal asthma medication use and isolated esophageal atresia (bronchodilator use: aOR = 2.39, 95%CI = 1.23, 4.66), isolated anorectal atresia (anti-inflammatory use: aOR = 2.12, 95%CI = 1.09, 4.12), and omphalocele (bronchodilator and anti-inflammatory use: aOR = 4.13, 95%CI = 1.43, 11.95).. Positive associations were observed for anorectal atresia, esophageal atresia, and omphalocele and maternal periconceptional asthma medication use, but not for other defects studied. It is possible that observed associations may be chance findings or may be a result of maternal asthma severity and related hypoxia rather than medication use.

Topics: Abnormalities, Drug-Induced; Adult; Albuterol; Anal Canal; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Anus, Imperforate; Asthma; Beclomethasone; Bronchodilator Agents; Case-Control Studies; Esophagus; Female; Fluticasone; Heart Defects, Congenital; Humans; Kidney; Limb Deformities, Congenital; Male; Middle Aged; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Radius; Risk Factors; Spine; Trachea; United States; Young Adult

Patients with chronic obstructive pulmonary disease (COPD) show a poor response to corticosteroids, which has been linked to oxidative stress. Here we show that the long-acting β(2) -agonist formoterol (FM) reversed corticosteroid insensitivity under oxidative stress via inhibition of phosphoinositide-3-kinase (PI3K) signalling.. Responsiveness to corticosteroids dexamethasone (Dex), budesonide (Bud) and fluticasone propionate (FP) was determined, as IC(50) values on TNF-α-induced interleukin 8 release, in U937 monocytic cell line treated with hydrogen peroxide (H(2) O(2) ) or peripheral blood mononuclear cells (PBMCs) from patients with COPD or severe asthma.. PBMCs from severe asthma and COPD were less sensitive to Dex compared with those from healthy subjects. Both FM (10(-9)  M) and salmeterol (SM, 10(-8)  M) reversed Dex insensitivity in severe asthma, but only FM restored Dex sensitivity in COPD. Although H(2) O(2) exposure decreased steroid sensitivity in U937 cells, FM restored responsiveness to Bud and FP while the effects of SM were weaker. Additionally, FM, but not SM, partially inhibited H(2) O(2) -induced PI3Kδ-dependent (PKB) phosphorylation. H(2) O(2) decreased SM-induced cAMP production in U937 cells, but did not significantly affect the response to FM. The reduction of SM effects by H(2) O(2) was reversed by pretreatment with LY294002, a PI3K inhibitor, or IC87114, a PI3Kδ inhibitor.. FM reversed oxidative stress-induced corticosteroid insensitivity and decreased β(2) adrenoceptor-dependent cAMP production via inhibition of PI3Kδ signalling. FM will be more effective than SM, when combined with corticosteroids, for the treatment of respiratory diseases under conditions of high oxidative stress, such as in COPD.

Topics: 1-Phosphatidylinositol 4-Kinase; Adenine; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Albuterol; Androstadienes; Asthma; Budesonide; Chromones; Dexamethasone; Drug Resistance; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Hydrogen Peroxide; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Morpholines; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Quinazolines; Receptors, Adrenergic, beta-2; Salmeterol Xinafoate; U937 Cells; Young Adult

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenal Insufficiency; Albuterol; Androstadienes; Asthma; Child; Child, Preschool; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Growth; Humans; Hydrocortisone; Male

Asthma is a common chronic disease characterized by airway inflammation and structural remodeling. Vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, is elevated in asthma patients. VEGF contributes to airway responsiveness and remodeling. It has been shown that treatment of asthma patients decreases VEGF levels, and inhibition of VEGF diminishes asthma symptoms in mice. Therefore, polymorphisms in the vascular endothelial growth factor A (VEGFA) gene might be associated with asthma treatment response.. This study enrolled 131 children with asthma treated with different therapies - specifically, the inhaled corticosteroid (ICS) fluticasone propionate or the leukotriene receptor antagonist (LTRA) montelukast. We performed an association analysis between improvement of lung function - assessed by measurement of the percentage of the predicted forced expiratory volume in 1 second (%predicted FEV(1)), the ratio between the FEV(1) and the forced vital capacity (FEV(1)/FVC) after 6 and 12 months of treatment, and asthma control after 12 months of treatment - and two polymorphisms, rs2146323 and rs833058, in the VEGFA gene.. Polymorphism rs2146323 A>C in VEGFA was associated with response to ICS therapy. Asthma patients with the AA genotype had a greater improvement in the %predicted FEV(1) than those with the AC or CC genotype (p = 0.018). Conversely, the AA genotype in rs2146323 was associated with uncontrolled asthma in patients regularly receiving LTRA therapy (p = 0.020) and a worse FEV(1)/FVC ratio in patients who episodically used LTRA therapy (p = 0.044). Furthermore, polymorphism rs833058 C>T was associated with treatment response to episodically used LTRA therapy. A subgroup of patients with the TT genotype had an improvement in the %predicted FEV(1), compared with no improvement in patients with the CT or CC genotype (p = 0.029).. Our results showed that treatment response to commonly used asthma therapies (ICS or LTRA) is associated with polymorphisms rs2146323 and rs833058 in VEGFA. With additional replication of this preliminary study, our findings could contribute to the development of individualized asthma therapy.

Topics: Acetates; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Cyclopropanes; Female; Fluticasone; Forced Expiratory Volume; Humans; Male; Polymorphism, Single Nucleotide; Quinolines; Sulfides; Treatment Outcome; Vascular Endothelial Growth Factor A

Topics: Airway Resistance; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchi; Bronchodilator Agents; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Glucocorticoids; Humans; Male; Muscle, Smooth; Muscle, Smooth, Vascular; Salmeterol Xinafoate; Vasodilation

Long-term inhaled corticosteroids are the preferred treatment for asthma, but their safety still controversial. The aim of the present study was to explore the effects of inhaled corticosteroids on bone age and growth in children with asthma.. Seventy-three children with asthma received inhaled fluticasone treatment at a starting dosage of 250 μg/d for 3 months, when the dosage was reduced by a third. Three months later, the patients were treated with fluticasone at a dosage of 125 μg/d for 6 months. Bone age, heights and weights were measured before and one year of treatment.. The increase in the heights, weights and RUS (radius, ulna and short finger bones) bone age of the children with asthma after one year of treatment was not significantly different from healthy children. There were no significant differences in body mass index (BMI) before and after one year of treatment, however the level of carpal bone age [-0.2(-0.6,0.8) years] was delayed after therapy compared to before treatment [-0.5(-1.0,0.6) years] (P<0.05).. Treatment with inhaled corticosteroids for 1 year may suppress the level of carpal bone age, but the level of RUS bone age, heights, weights and BMI are not affected. It is necessary to monitor the growth of children with asthma who receive long-term inhaled corticosteroid treatment.

Topics: Administration, Inhalation; Age Determination by Skeleton; Androstadienes; Asthma; Body Height; Body Mass Index; Body Weight; Bone Development; Child; Child, Preschool; Female; Fluticasone; Humans; Male

Recent studies suggest that airway smooth muscle remodeling is an early event in the course of asthma. Little is known of the effects of long-term antigen avoidance and inhaled corticosteroids on chronically established airway remodeling. We sought to measure the effects of inhaled corticosteroids and antigen avoidance on airway remodeling in the peripheral airways of horses with heaves, a naturally occurring asthma-like disease. Heaves-affected adult horses with ongoing airway inflammation and bronchoconstriction were treated with fluticasone propionate (with and without concurrent antigen avoidance) (n = 6) or with antigen avoidance alone (n = 5). Lung function and bronchoalveolar lavage were performed at multiple time points, and peripheral lung biopsies were collected before and after 6 and 12 months of treatment. Lung function improved more quickly with inhaled corticosteroids, but eventually normalized in both groups. Inflammation was better controlled with antigen avoidance. During the study period, corrected smooth muscle mass decreased from 12.1 ± 2.8 × 10(-3) and 11.3 ± 1.2 × 10(-3) to 8.3 ± 1.4 × 10(-3) and 7.9 ± 1.0 × 10(-3) in the antigen avoidance and fluticasone groups, respectively (P = 0.03). At 6 months, smooth muscle mass was significantly smaller compared with baseline only in the fluticasone-treated animals. The subepithelial collagen area was lower at 12 months than at baseline in both groups. During the study period, airway smooth muscle remodeling decreased by approximately 30% in both groups, although the decrease was faster in horses receiving inhaled corticosteroids. Inhaled corticosteroids may accelerate the reversal of smooth muscle remodeling, even if airway inflammation is better controlled with antigen avoidance.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Airway Remodeling; Airway Resistance; Androstadienes; Animals; Antigens, Plant; Asthma; Bronchioles; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Cell Proliferation; Collagen; Cytokines; Fluticasone; Horse Diseases; Horses; Inflammation Mediators; Lung; Monocytes; Muscle, Smooth; Organ Size; Proliferating Cell Nuclear Antigen; Respiratory Function Tests; Respiratory Mucosa; Treatment Outcome

Behavioural changes, such as hyperactivity, aggression, mood swings and agitation may occur during the use of inhaled corticosteroids. Children are particularly vulnerable to this possible adverse drug reaction. As this side effect is reversible, timely recognition is important in order to prevent unnecessary diagnostic investigations and problems at home or at school. In this article we present two patients, a seven-year-old boy and a nine-year-old girl, who illustrate the importance of awareness of this unwanted effect of inhaled corticosteroids.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Child; Female; Fluticasone; Humans; Male; Psychomotor Agitation

The influence of dentures on residual inhaled corticosteroids (ICSs) in the mouths of elderly asthmatic patients and the appropriate time for gargling after inhaling ICSs are unclear.. Twenty elderly patients in whom moderate persistent asthma was stably controlled using fluticasone propionate Diskus (FP, n = 10) or hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP, n = 10) for more than 3 months and who wore dentures daily were switched to the other type of ICS for 4 weeks in a crossover manner. The residual amount of each ICS in their mouths after inhalation was measured along with determination of peak inspiratory flow (PIF) and pharyngeal culture for detecting Candida albicans.. The total amounts of residual ICSs in gargling fluids (μg) with HFA-BDP were significantly greater than those with FP (15.6 ± 14.6 vs. 11.5 ± 13.8, p = 0.028). The residual amounts of HFA-BDP were significantly greater in the patients with complete dentures than in those with partial dentures. The residual amounts of FP were significantly correlated with the PIF values in the FP treatment (p = 0.013) but not in the HFA-BDP treatment (p = 0.202). No residual ICSs remained after the third gargling in either treatment. The occurrence of candidiasis during the HFA-BDP period was significantly higher than that during the FP treatment (p = 0.046).. The dentures of elderly asthmatics affect the oral residues of ICSs and occurrence of candidiasis in HFA-BDP treatment; meanwhile, the PIF values affected these factors in FP treatment. Three times gargling after inhaling ICSs is required.

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Androstadienes; Asthma; Beclomethasone; Bronchodilator Agents; Candidiasis, Oral; Dentures; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Male; Mouth; Mouthwashes

The objective of this study is to determine the effects of the long-term treatment with inhaled fluticasone propionate on osteocalcin, cortisol levels, and bone mineral status in children with asthma.. This cross-sectional study examined 230 prepubertal children with asthma (aged 6–11) who had intermittently used inhaled fluticasone propionate for at least 5 years at a mean daily dose of 200 μg (range: 200-350 μg). Serum osteocalcin, cortisol, and bone mineral density (BMD) of the lumbar spine were obtained from each participant. The control group consisted of gender- and age-matched children (n = 170) who were newly diagnosed with asthma and who were not being treated with corticosteroid.. The average age (± SEM) was 8.9 ± 0.7 years, their mean (± SEM) daily steroid dose was 180.3 ± 55.0 μg, with 236.5 ± 17.2 g total steroid use during treatment. Between the study and the control groups, no significant differences were observed in cortisol, osteocalcin levels, and BMD (p > 0.05).. Long-term treatment with inhaled fluticasone propionate (100 μg twice daily) revealed no negative effects on serum osteocalcin, cortisol levels, and BMD in children with asthma.

Topics: Administration, Inhalation; Androstadienes; Asthma; Bone Density; Bronchodilator Agents; Case-Control Studies; Child; Cross-Sectional Studies; Female; Fluticasone; Humans; Hydrocortisone; Male; Osteocalcin; Puberty; Time Factors

To assess prevalence of behavioural problems in preschool children with asthma with electronically verified exposure to inhaled corticosteroids (ICS).. Cross-sectional study of 81 children 2-5 years of age using daily ICS for persistent asthma. During 3 months' follow-up, adherence to ICS treatment was recorded by an electronical logging device (Smartinhaler(®)). Parents completed the Child Behavior Checklist 1.5-5 years (CBCL 1.5-5) to assess behavioural problems; results were compared to a published reference group of healthy children.. The median (interquartile range) adherence to ICS was 92 (78-97) %. There was no difference in total CBCL score between children with asthma on ICS (mean, [SD] 32.10 [1.99]) and the reference group (33.30 [1.87], 95% CI for difference -6.62 to 4.22). Children with asthma were more likely to have somatic complaints (95% CI for difference 0.64 to 1.96) and less likely to have anxious/depressive symptoms (95% CI for difference -1.57 to -0.25) than the reference group. CBCL scores were not significantly related to the electronically measured adherence rates.. Maintenance treatment with ICS, taken daily as prescribed, is not associated with an increased risk of behavioural problems in preschool children.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Child Behavior Disorders; Child, Preschool; Chronic Disease; Cross-Sectional Studies; Drug Administration Schedule; Female; Fluticasone; Follow-Up Studies; Humans; Logistic Models; Maintenance Chemotherapy; Male; Medication Adherence; Prevalence; Surveys and Questionnaires; Treatment Outcome

Topics: Adult; Age of Onset; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Female; Fluticasone; Humans; Male; Salmeterol Xinafoate; Treatment Outcome

To study a relationship of the characteristics of simple and complex visual sensorimotor reactions to asthma controllability in middle-aged and elderly outpatients during disease-modifying antirheumatic drug therapy with beclomethasone, fluticasone, or budesonide in average and high daily doses.. Eighty middle-aged and elderly patients with asthma were examined. The level of asthma control, the main parameters of external respiratory function, and the characteristics of simple and complex visual sensorimotor reactions were assessed.. Uncontrolled asthma was observed in more than 50% of the asthmatic patients in the outpatient setting. Moderate linear relationships were found between the main physiological parameters and the level of the standard asthma control test.. In the patients with controlled asthma, the latent periods of simple and complex visual sensorimotor reactions were significantly shorter than in those with poorly controlled asthma.

Topics: Administration, Inhalation; Adult; Aged; Androstadienes; Antirheumatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Female; Fluticasone; Glucocorticoids; Humans; Long-Term Care; Male; Middle Aged; Outpatients; Psychomotor Performance

Pre-clinical evaluation of asthma therapies requires animal models of chronic airways inflammation, airway hyperresponsiveness (AHR) and lung remodelling that accurately predict drug effectiveness in human asthma. However, most animal models focus on acute allergen challenges where chronic inflammation and airway remodelling are absent. Chronic allergen challenge models have been developed in mice but few studies use guinea-pigs which may be more relevant to humans. We tested the hypothesis that a chronic rather than acute pulmonary inflammation model would best predict clinical outcome for asthma treatments. Guinea-pigs sensitized with ovalbumin (OVA) received single (acute) or nine OVA inhalation challenges at 48 h intervals (chronic). Airways function was recorded as specific airways conductance (sG(aw)) in conscious animals for 12 h after OVA challenge. AHR to inhaled histamine, inflammatory cell influx and lung histology were determined 24 h after the single or 9th OVA exposure. The inhaled corticosteroid, fluticasone propionate (FP), the phosphodiesterase 4 inhibitor, roflumilast, and the inducible nitric oxide synthase (iNOS) inhibitor, GW274150, orally, were administered 24 and 0.5 h before and 6 h after the single or final chronic OVA exposure. Both models displayed early (EAR) and late (LAR) asthmatic responses to OVA challenge, as falls in sG(aw), AHR, as increased histamine-induced bronchoconstriction, and inflammatory cell influx. Tissue remodelling, seen as increased collagen and goblet cell hyperplasia, occurred after multiple OVA challenge. Treatment with FP and roflumilast inhibited the LAR, cell influx and AHR in both models, and the remodelling in the chronic model. GW274150 also inhibited the LAR, AHR and eosinophil influx in the acute model, but not, together with the remodelling, in the chronic model. In the clinical setting, inhaled corticosteroids and phosphodiesterase 4 inhibitors are relatively effective against most features of asthma whereas the iNOS inhibitor GW274150 was ineffective. Thus, while there remain certain differences between our data and clinical effectiveness of these antiasthma drugs, a chronic pulmonary inflammation guinea-pig model does appear to be a better pre-clinical predictor of potential asthma therapeutics than an acute model.

Topics: Acute Disease; Administration, Inhalation; Administration, Oral; Aminopyridines; Androstadienes; Animals; Anti-Asthmatic Agents; Asthma; Benzamides; Bronchial Hyperreactivity; Chronic Disease; Cyclopropanes; Disease Models, Animal; Fluticasone; Guinea Pigs; Histamine; Inflammation; Male; Ovalbumin; Sulfides; Time Factors

Topics: Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Budesonide; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Salmeterol Xinafoate; Treatment Outcome

Topics: Alleles; Androstadienes; Asthma; Bronchodilator Agents; Child, Preschool; Chromosomes, Human, Pair 7; Dermatitis, Perioral; DNA Mutational Analysis; Epilepsies, Myoclonic; Exocrine Pancreatic Insufficiency; Failure to Thrive; Female; Fluticasone; Humans; Infant; Male; Metered Dose Inhalers; NAV1.1 Voltage-Gated Sodium Channel; Status Epilepticus; Syndrome

Salmeterol, a long-acting β2-adrenergic receptor agonist used for the treatment of asthma and chronic obstructive pulmonary disease, has an adverse effects profile that is similar to that of salbutamol and other β2-agonists. We report a sympathomimetic syndrome with metabolic acidosis and hyperlactatemia after intentional inhalation of salmeterol in a suicide attempt. A 16-year-old female patient was admitted to the emergency department approximately 2 hours after having inhaled 60 puffs of a combination of salmeterol xinafoate 25 μg and fluticasone propionate 50 μg. She presented in an anxious state with complaints of palpitations and chest pain. The electrocardiogram demonstrated sinus tachycardia and ST-segment depression in the inferior and anterolateral leads. Laboratory findings showed hypokalemia, hypophosphatemia, and lactic acidosis. Cardiac troponin I and creatine kinase MB remained within the normal range. Treatment was supportive and included intravenous fluids and cautious potassium supplementation. The next day, electrocardiographic and laboratory findings returned to normal. We hypothesize that stimulation of β2-adrenergic receptors by inhalation of salmeterol caused this patient's lactic acidosis. This observation is consistent with the hypothesis that the hyperlactatemia observed during asthma attacks is due in part to the administration of high doses of β2-agonists. Salmeterol overdose by inhalation appears to be sufficient to cause lactic acidosis.

Topics: Acidosis, Lactic; Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Drug Administration Schedule; Drug Overdose; Drug Therapy, Combination; Female; Fluid Therapy; Fluticasone; Humans; Intention; Lactic Acid; Potassium; Salmeterol Xinafoate

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Drug Administration Schedule; Drug Combinations; Ethanolamines; Fluticasone; Formoterol Fumarate; Guideline Adherence; Humans; Randomized Controlled Trials as Topic

Topics: Androstadienes; Asthma; Bronchodilator Agents; Clinical Trials as Topic; Drug Therapy, Combination; Ethanolamines; Evidence-Based Medicine; Fluticasone; Formoterol Fumarate; Humans; Italy; Nasal Sprays; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Asthma; Body Height; Corticosterone; Fluticasone; Glucocorticoids; Growth Disorders; Humans; Infant; Male

Inhaled corticosteroids (ICS) are the mainstay of asthma treatment. Studies in chronic obstructive pulmonary disease reported increased rates of pneumonia with ICS. Concerns exist about an increased pneumonia risk in patients with asthma taking ICS.. To evaluate the risks of pneumonia in patients with asthma taking ICS.. A retrospective analysis evaluated studies of the ICS budesonide in asthma. The primary data set were all double-blind, placebo-controlled trials lasting at least 3 months, involving budesonide (26 trials, n = 9,067 for budesonide; n = 5,926 for the comparator) sponsored by AstraZeneca. A secondary data set evaluated all double-blind trials lasting at least 3 months but without placebo control (60 trials, n = 33,496 for budesonide, n = 2,773 for fluticasone propionate). Cox proportional hazards regression modeling was used to estimate the relative effect of ICS on pneumonia adverse events (AEs) or serious adverse events (SAEs).. In the primary data set, the occurrence of pneumonia AEs was 0.5% (rate 10.0 events/1,000 patient-years [TPY]) for budesonide and 1.2% (19.3 per TPY) for placebo (hazard ratio, 0.52; 95% confidence interval, 0.36-0.76; P < 0.001); the occurrence of pneumonia SAEs was 0.15% (2.9 per TPY) for budesonide and 0.13% (2.1 per TPY) for placebo (hazard ratio, 1.29; 95% confidence interval, 0.53-3.12; P = 0.58). In the secondary data set, the percentage of patients reporting pneumonia AEs was 0.70% (12.7 per TPY), whereas the percentage of patients reporting pneumonia SAEs was 0.17% (3.1 per TPY). There was no increased risk with higher budesonide doses or any difference between budesonide and fluticasone.. There is no increased risk of pneumonia in patients with asthma, identified as an AE or SAE, in clinical trials using budesonide.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Asthma; Bronchodilator Agents; Budesonide; Causality; Child; Child, Preschool; Comorbidity; Double-Blind Method; Female; Fluticasone; Humans; Incidence; Male; Middle Aged; Pneumonia; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Young Adult

Although systemic, topical, and periocular corticosteroid administration have long been associated with ocular side effects, there has been little evidence to suggest that long-term inhaled corticosteroids can cause ocular side effects. The aim of this study was to evaluate the effects of long term treatment inhaled fluticasone propionate spray usage the recommended dose on some ocular functions in pediatric patients with asthma.. The study group consisted of 266 prepubertal children with asthma who had used inhaled fluticasone propionate spray at 3-6 years intermittently. One hundred and sixty children who were newly diagnosed with asthma without any treatment made up the control group. Schirmer test results, central corneal thickness, visual acuity, intraocular pressure, cataract formation, keratometry and tear break-up time compared between study and control groups.. The ages of the 266 study patients (150 male) were between 7 and 11 years. The average age (±SEM) was 8.2±1.7 years, and the mean (±SEM) a daily dose of 323 μg (range 250-450 μg) inhaled fluticasone propionate spray, with 865.2±215 g total steroid use during treatment. Eye functions including cataract formation, corneal ectasia, ocular hypertension or glaucoma, and dry eye were not observed in any of the patients in the study group and were not correlated with total steroid dosage (t=0.150, p=0.384).. Our findings suggest that long-term intermittent treatment for 3-6 years with inhaled fluticasone propionate spray, as much as average 320 μg daily, in children with asthma seems to be safe for some eye functions.

Topics: Androstadienes; Asthma; Bronchodilator Agents; Case-Control Studies; Child; Female; Fluticasone; Humans; Intraocular Pressure; Male; Rhinitis, Allergic, Perennial; Tears; Time Factors; Visual Acuity

Long-term immunosuppression with oral corticosteroids is frequently used to treat inflammatory diseases of the lung and is advocated in the management of some patients with asthma.. The authors describe the case of a 35-year-old man with severe refractory asthma who developed a slowly progressive thoracic spinal cord syndrome.. Spinal imaging demonstrated the presence of spinal epidural lipomatosis, a rare complication of prolonged corticosteroid therapy, which is characterized by overgrowth of fat in the epidural space and neuronal compression.. Spinal epidural lipomatosis should be considered in patients receiving long-term corticosteroid therapy who develop symptoms and signs suggestive of spinal cord compression.

Topics: Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Epidural Space; Fatal Outcome; Fluticasone; Humans; Lipomatosis; Magnetic Resonance Imaging; Male; Prednisolone